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Introduction: Ethion is an organophosphate used as an acaricide and insecticide, that is restricted worldwide. In Colombia, pesticide poisoning is the third most common cause of chemical intoxication. On 9 October 2022, an outbreak of ethion poisoning occurred in Pereira. The aim of this study was to describe the clinical and epidemiological characteristics of the outbreak. Methods: This is a descriptive study of an outbreak of organophosphate poisoning. The onset of symptoms occurred on 9 October 2022, following the consumption of empanadas. Information was collected on sociodemographic characteristics and clinical manifestations, as well as from paraclinical examinations. Data were obtained from clinical histories, field epidemiological investigations, and inspection visits. Food samples were collected for analysis by gas chromatography-mass spectrometry. Attack rates, proportions, and measures of central tendency, dispersion, and position were calculated. Results: The case definition was met by 37 individuals with a median age of 30 years; all presented with muscarinic symptoms, 29 patients presented with nicotinic symptoms, and 20 patients presented with neurological symptoms. Males were the most affected (57%), and the most common time of symptom onset was 10:00 am. Twenty-three patients (62%) required intensive care unit admission, of whom 14 (38%) required mechanical ventilation. No deaths were reported. Erythrocyte acetylcholinesterase activity was reduced in all patients. Ethion was detected in mass-prepared maize and empanadas at concentrations greater than 0.1 mg/kg. The consumption of empanadas was identified as the common source. Discussion: In Colombia, pesticide poisonings are the third most common type of poisoning caused by chemical substances reported to the National Health Institute through the National Public Health Surveillance System. In the present outbreak, ethion was in empanadas, likely due to contamination of cooking oil. Conclusions: We describe a large ethion-contaminated food poisoning outbreak reported in Colombia. The main symptoms were muscarinic, and the main treatment measures employed were atropine and respiratory support. Increased awareness of pesticide poisoning and training for food handlers are needed. [ABSTRACT FROM AUTHOR]

The uncontrolled use of pesticides signifies a substantial health hazard. This study was designed to explore the prognostic role of on-admission hepatic aminotransferases [alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and the reversed De Ritis ratio (ALT/AST)] in the prediction of in-hospital mortality among patients with acute organophosphate (OP) poisoning. We conducted a retrospective study based on extracting the required information from the specific medical records for acutely OP-intoxicated patients admitted to the intensive care unit. A total of 49 acutely malathion-intoxicated patients were enrolled in the study. The in-hospital mortality rate was 32.7%. Patients were stratified into survivors and non-survivors. Compared to the survivors, the non-survivors had significantly lower Glasgow coma scale scores, mean arterial blood pressure, significantly higher reversed De Ritis ratio (ALT/AST), and ALT and AST activities. The reversed De Ritis ratio (ALT/AST) and ALT demonstrated good discrimination between the survivors and the non-survivors with an area under the curve (AUC) of 0.708 vs 0.781, respectively, however, AST showed satisfactory discrimination, AUC of 0.694. Hepatic aminotransferases are useful in predicting in-hospital mortality in acute OP poisoning. ALT is the most specific biomarker. However, the reversed De Ritis ratio (ALT/AST) is the most sensitive one. [ABSTRACT FROM AUTHOR]

We designed this study to identify the factors associated with time to successful weaning in mechanically ventilated organophosphate (OP)-poisoned patients as the primary outcomes while duration of mechanical ventilation (MV) support, intensive care unit (ICU), and hospital length of stay (LOS) and in-hospital mortality as the secondary outcomes. We conducted a retrospective study of mechanically ventilated OP-poisoned patients admitted to the ICU of Poison Control Center of Ain Shams, Cairo, Egypt, starting from January 2019 to December 2019. Weaning was considered successful if the patient succeeded in the first spontaneous breathing trial of weaning and did not need reinstitution of MV. We used Cox proportional hazards regression models to identify factors associated with time to successful weaning in the studied patients. A total of 55 patients were enrolled in the study. Thirty-eight patients were weaned successfully. Lower initial red cell distribution width (RDW) levels [adjusted hazard ratio (HR), 0.299, 95% confidence interval (CI) (0.184–0.486)] and lower initial doses of atropine [adjusted HR, 0.97, 95% CI (0.935–0.999)] were independently associated with shorter time to achieve successful weaning. Successfully weaned patients had significantly longer hospital LOS (p = 0.019) and no reported in-hospital mortality (p < 0.001) compared with patients who failed to wean. We concluded that initial RDW and initial doses of atropine were found to be the strongest factors associated with time to successful weaning in mechanically ventilated OP-poisoned patients. RDW and atropine can be used as simple risk assessment tools in OP poisoning. [ABSTRACT FROM AUTHOR]

To evaluating the efficacy of fresh frozen plasma (FFP) in comparison with conventional regimen in the treatment of organophosphate (OP) poisoning. 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. 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)]. 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. [ABSTRACT FROM AUTHOR]

Context: Nerve agents like sarin or VX have repeatedly been used in military conflicts or homicidal attacks, as seen in Syria or Malaysia 2017. Together with pesticides, nerve agents assort as organophosphorus compounds (OP), which inhibit the enzyme acetylcholinesterase. To counteract subsequent fatal symptoms due to acetylcholine (ACh) accumulation, oximes plus atropine are administered, a regimen that lacks efficacy in several cases of OP poisoning. New therapeutics are in development, but still need evaluation before clinical employment. Supportive treatment with already approved drugs presents an alternative, whereby compounds from COPD and asthma therapy are likely options. A recent pilot study by Chowdhury et al. included β2-agonist salbutamol in the treatment of OP-pesticide poisoned patients, yielding ambiguous results concerning the addition. Here, we provide experimental data for further investigations regarding the value of these drugs in OP poisoning. Methods: By video-microscopy, changes in airway area were analyzed in VX-poisoned rat precision cut lung slices (PCLS) after ACh-induced airway contraction and subsequent application of selected anticholinergics/β2-agonists. Results: Glycopyrrolate and ipratropium efficiently antagonized an ACh-induced airway contraction in VX-poisoned PCLS (EC50 glycopyrrolate 15.8 nmol/L, EC50 ipratropium 2.3 nmol/L). β2-agonists formoterol and salbutamol had only negligible effects when solely applied in the same setting. However, combination of formoterol or salbutamol with low dosed glycopyrrolate or atropine led to an additive effect compared to the sole application [50.6 ± 8.8% airway area increase after 10 nmol/L formoterol +1 nmol/L atropine versus 11.7 ± 9.2% (10 nmol/L formoterol) or 8.6 ± 5.9% (1 nmol/L atropine)]. Discussion: We showed antagonizing effects of anticholinergics and β2-agonists on ACh-induced airway contractions in VX-poisoned PCLS, thus providing experimental data to support a prospective comprehensive clinical study. Conclusions: Our results indicate that COPD and asthma therapeutics could be a valuable addition to the treatment of OP poisoning. [ABSTRACT FROM AUTHOR]

Introduction: Organophosphate (OP) poisoning is an important public health concern in South-Asia especially in the farming population. Treatment of OP poisoning has remained unchanged since decades and case fatality is 10–40% despite best supportive care, anticholinergic agents and oximes. A new antidote is the need of the hour. Lipid emulsion being inexpensive, easily available and effective in management of other lipid soluble toxins may be a novel option. However, safety has not been established and efficacy is limited to animal studies and case reports in humans with OP poisoning. Methods: An open-label pilot study was undertaken to establish the safety of lipid emulsion in OP poisoning. Patients with symptomatic OP poisoning, meeting the inclusion and exclusion criteria were treated with 100 mL of 20% intravenous lipid emulsion (after consent) in addition to standard of care. They were monitored for change in hemodynamic parameters, change in hematology and biochemical parameters at various intervals of time after initiation of therapy. Morbidity, mortality, and occurrence of adverse effects were compared with historical control group. Results: Forty patients with symptomatic OP poisoning were enrolled in the study group. No significant change in hemodynamic parameters (pulse rate, systolic, diastolic blood pressure, and mean arterial pressure) or in hematology and biochemical parameters were seen. No adverse effects were noted. Compared to historical controls, no change in mortality was noted, although there was reduced duration of mechanical ventilation, hospital stay, and early resolution of hypernatremia. Conclusions: This study evaluates the safety of lipid emulsion in OP poisoning. Absence of change in hemodynamic parameters and adverse effects suggests lipid emulsion may be safe for this indication. Large randomized controlled trials are now required to assess clinical efficacy. ClinicalTrials.gov number: NCT03564574 [ABSTRACT FROM AUTHOR]

Organophosphorus nerve agents (OPs) are potent irreversible inhibitors of acetylcholinesterase (AChE). They cause a major cholinergic syndrome. Most progress in medical counter-measures of OP poisoning was achieved more than 30 years ago with pyridinium oximes as AChE reactivators, anticholinergic drugs and benzodiazepines as neuroprotectants in emergency treatments, and carbamates for pretreatments. Counter-measures ensure protection of peripheral nervous system and mitigate acute effects lethal doses of agents. However, pyridostigmine and oximes do not protect/reactivate central AChEs. Moreover, oximes do not reactivate AChEs inhibited by phosphoramidates like tabun. In addition, current drugs are not sufficiently effective in protecting central nervous system against seizures-induced irreversible brain damage. New therapeutic approaches involve: detoxification of OP molecules before they reach targets by administrating bioscavengers; protection/reactivation of central AChEs by drugs capable of crossing the blood brain barrier; neuroprotection with multifunctional drugs; improvement of delayed therapy using anti-NMDA drugs. Future developments are aimed at optimizing treatments of acute, intermediate and delayed toxicity. This implies identification of unkown OP targets and toxicity mechanisms, research on drug nanocarriers and alternative routes for delivery. Therapies of the future, gene therapy for transient production of bioscavengers and cell therapy for neuronal regeneration are still in infancy for practical medical uses. [ABSTRACT FROM PUBLISHER]

Purpose. Organophosphate poisoning (OPP) accounts for 200,000 deaths annually in developing countries. Serum cholinesterase (SChE) is of diagnostic value in patients with OPP and is checked repeatedly during the course of treatment. This study aimed to investigate the recovery pattern in patients with OPP using linear mixed models. Methods. Using a retrospective cohort study design, we included 212 adult OPP patients who had visited the emergency department (ED) in a tertiary medical center between 2000 and 2010. One hundred and thirty-one patients were available for analysis, as 81 patients did not meet the criteria and were excluded. Information regarding basic personal characteristics, initial vital signs and severity scores, laboratory data, type and amount of organophosphate ingested, treatment, and serial SChE values was collected. A random coefficient model with a random intercept and a random slope of time were added to address the dynamic relationships of SChE with time and other associated factors. Results. The initial SChE activity and recovery rates varied among patients with OPP. The type of organophosphate, the first SChE activity, and the initial APACHE II score were significantly related to the SChE recovery trend. Chlorpyrifos and methamidophos had significantly slower and faster SChE recovery rates, respectively, than other organophosphates. Sex, dose of Pralidoxim (2-PAM), and delay in obtaining medical assistance did not significantly affect SChE recovery. Conclusions. This study demonstrated the pattern and associated correlates of SChE activity recovery in patients with acute OPP. Chlorpyrifos appeared to have a slower SChE activity recovery rate than other organophosphates. [ABSTRACT FROM AUTHOR]

Context. Exposure of children to pesticides and overt poisoning are an increasingly important problem in South Africa. Objective. This study describes the profile of acute paediatric pesticide exposures and poisonings presenting to Red Cross War Memorial Children's Hospital (RCWMCH) in Cape Town South Africa from 2003 to 2008, identifies those poisonings due to illicit pesticides sold on the streets ('street pesticides') and assesses the number of incidents in which the statutory requirement of notification to the local health authority is met. Methods. Cases were identified by review of the RCWMCH case and notification records and the local health authority notification records. Results. There were 306 patients with 311 incidents of acute pesticide exposure or poisoning. This represents 11% of all paediatric exposures and poisonings (N = 2868) seen over the 6-year period. The number of pesticide incidents increased annually. Two hundred seventy-eight (91%) children were under 6 years old and 164 (54%) were males. Two hundred seventeen (70%) patients came from six socio economically diverse suburbs in the Cape Town Metropole, each of which ranges from informal settlements with extreme poverty to formal housing with lower to middle class populations. There was a summer predominance of acute pesticide exposures and poisonings. The commonest group of pesticides were 203 cholinergics (includes organophosphates and carbamates), 35 anticoagulants and 45 unknowns. One hundred incidents were classified as exposures as they were asymptomatic. Two hundred eleven symptomatic incidents, termed pesticide poisonings, required admission; 121 to High Care or Intensive Care Unit (ICU). The median length of stay in hospital was 3 days (range 0-52). There were 6 (2%) deaths. The large group of cholinergic exposures and poisonings (203) required 195 (96%) admissions; 120 (59%) to High Care or ICU. Of the 44 'street pesticide' exposures and poisonings, 33 were cholinergic poisonings and 21 required High Care or ICU. Eighty-seven (41%) of 211 poisonings requiring notification were recorded at the local health authority; all were instances of cholinergic poisoning. Conclusion. The increasing number and the morbidity and mortality of acute paediatric pesticide exposure and poisoning is of great concern. Furthermore, the magnitude of the problem is masked by inadequate notification with the relevant health authorities. [ABSTRACT FROM AUTHOR]

Objective. The effects of obidoxime in the treatment of organophosphate poisoning were assessed by biochemical and biological effect monitoring. In this article we report effects on neuromuscular function, oxime and atropine concentration, and relate them to acetylcholinesterase (AChE) activity. Methods. We measured the activity of cholinesterase in plasma and AChE in red blood cells (RBC) and related these data with neuromuscular transmission analysis (ulnar nerve stimulation). Concomitantly, poison and oxon along with plasma obidoxime and atropine levels were measured at regular intervals. Results. We found a close correlation between RBC–AChE activity and neuromuscular transmission and a reciprocal correlation between both the atropine maintenance dose and/or its plasma concentration. The steady state of RBC–AChE activity of reactivation and re-inhibition followed the course predicted by laboratory-determined reaction constants. Conclusions. Intense monitoring of organophosphate-poisoned patients allowed assessment of why a given obidoxime concentration was, or was not, able to counteract the re-inhibition of the RBC–AChE. RBC–AChE activity mirrors the function of n-receptor- and m-receptor-mediated cholinergic signaling as measured by neuromuscular transmission and atropine requirements. [ABSTRACT FROM AUTHOR]

Organophosphate poisoning in the context of self-harm is a common medical emergency in Asia. Prolonged muscle weakness is an important but poorly understood cause of morbidity and mortality of the poisoning. This study examined mitochondrial function and its modulation by nitric oxide in muscle weakness of rats exposed to an acute, oral (0.8LD50) dose of monocrotophos. Muscle mitochondrial ATP synthase activity was inhibited in the rat in acute exposure to monocrotophos while respiration per se was not affected. This was accompanied by decreased mitochondrial uptake of calcium and increased levels of nitric oxide. Reactive cysteine groups of ATP synthase subunits were reduced in number, which may contribute to decreased enzyme activity. The decrease in ATP synthase activity and reactive cysteine groups of ATP synthase subunits was prevented by treatment of animals with the nitric oxide synthase inhibitor, L-NG Nitroarginine methyl ester, at 12 mg/kg body weight for 9 days in drinking water, prior to monocrotophos exposure. This indicated a role for nitric oxide in the process. The alterations in mitochondrial calcium uptake may influence cytosolic calcium levels and contribute to muscle weakness of acute organophosphate exposure. [ABSTRACT FROM AUTHOR]

Adult respiratory distress syndrome (ARDS) is a clinical syndrome which occurs due to various direct or indirect noxious agents and pyhsical mechanisms. One of the etiological factors is ingested chemicals (e.g. paraquat, ethylene glycol). The organophosphorous (OP) insecticides are the most toxic and frequently encountered chemicals that produce poisoning in humans. Studies were undertaken to investigate whether OP insecticides may produce ARDS. Fifteen autopsy cases due to suicidal OP insecticide poisoning were investigated. Toxicological analyses were performed with a gas chromatography-nitrogen phosphorous detector (GC-NPD). Methamidophos, dimefox and dichlorvos were the detected OP. Lungs were examined macroscopically. Two cases showed features compatible with ARDS in which the only cause of death was OP poisoning. Due to the severity of ARDS it is important to assess insecticidal exposure in an attempt to enhance survival patterns following OP poisoning in patients in order to initiate therapy. [ABSTRACT FROM AUTHOR]

Abnormal regional cerebral blood flow in patients with acute carbon monoxide (CO) and organophosphate (OP) poisoning was examined using 99m Tc-hexamethylpropylene amine oxime (HMPAO) brain single photon emission computed tomography (SPECT) in fourteen patients. We evaluated the predictive significance of acute phase brain SPECT findings for long-term neuropsychological sequelae. Changes were found in the frontal, temporal, parietal lobes within the first week after both types of poisoning. The distribution of the hypoperfused cerebral areas as demonstrated by 99m Tc-HMPAO imaging was similar in the two groups during the acute phase. Neuropsychological sequelae developed in five patients poisoned with OP and six with CO. Patients who had SPECT findings heterogeneously or in the temporal or frontal lobes displayed disorientation. Those with fronto-parietal and frontal lobe changes displayed mental confusion. Parkinsonism also was observed in patients with parieto-occipital, parietal and frontal lobe lesions. The distribution of these lesions appears to predict the long term sequelae of these poisonings, though additional studies with larger numbers of patients are needed to confirm the role of SPECT imaging in both OP and CO poisonings. [ABSTRACT FROM AUTHOR]

Organophosphate poisoning is a common method of deliberate self-harm in countries where the pesticides are readily available. The severity of neuroparalysis and myopathy occurring in acute organophosphate poisoned patients is determined by the severity of poisoning and is associated with morbidity and mortality. Molecular mechanisms that underlie severe paralysis are not well delineated but are essential to know to improve treatment. In this study rats were subjected to increasing doses (0.25 to 0.8 LD50) of monocrotophos, and cell membrane lipid profiles, particularly those of myofibril membranes, were examined in relation to neuromuscular weakness occurring in poisoning. Increasing doses of monocrotophos inhibited brain and RBC acetylcholinesterase &nvge;60% early in the poisoning. RBC acetylcholinesterase levels recovered to 70% to 80% of normal while brain acetylcholinesterase remained 44% to 67% inhibited 1 week after poisoning. Increasing severity of poisoning led to significant changes in myofibril membrane lipid composition with cholesterol to phospholipid ratios increasing from 0.029 ± 0.008 in controls to 0.063 ± 0.023 in severe poisoning (p > 0.05). These changes were associated with neuromuscular weakness in the first day of poisoning. Membrane changes were reversible and rats recovered muscle strength in 1 week with no treatment. Lipid compositions of the intestine, brain, and muscle mitochondrial membranes were not affected by monocrotophos. The study indicated that neuromuscular weakness was associated with muscle membrane disorganization early in the course of acute organophosphate poisoning and that subclinical neurotoxicity of long duration may be a consequence of acute organophosphate poisoning. Controlling the severity of poisoning early in the course of acute organophosphate poisoning appears to be important for clinical recovery. [ABSTRACT FROM AUTHOR]

Objective . The aim of this study was to evaluate the Acute Physiology and Chronic Health Evaluation (APACHE) II, III and Simplified Acute Physiology Score II (SAPS II) as predictors of severity of organophosphate poisoning (OPP). Methods . This is a retrospective study of 48 patients with OPP who were admitted to the intensive care unit (ICU) for at least 24 h between 1997 and 2004. Demographic, laboratory, survival data and on day one APACHE II, III, SAPS II and Glasgow Coma Scale (GCS) were recorded, and correlations between these scores and severity of poisoning were performed. Results . Forty-eight patients were evaluated. Mechanical ventilation was required by 58% of patients. The mean APACHE II, III and SAPS II values were 11.5 ± 7.21, 42.1 ± 24.49 and 25.1 ± 15.76, respectively. Total dose and duration of atropine and of pralidoxime therapy, length of ICU stay and mortality all correlated with these clinical scoring tools. Conclusions . The APACHE II, III and SAPS II clinical scoring tools seem to predict the severity of organophosphate poisoning, and may have prognostic value. [ABSTRACT FROM AUTHOR]

Objectives. In Taiwan, the widespread use of organophosphates(OPs) in agricultural and household environments results in numerous OP poisoning. To better understand the clinical significance of associated parameters on respiratory failure and patient outcome, we evaluate patients admitted to the Nephrology ward in our hospital with OP intoxication. Patients and METHODS: Over a period of 2 years, a total of 42 consecutive patients with OP poisoning admitted to the nephrology ward or the Intensive Care Unit of Chang-Gung Memorial Hospital were the subjects in the study. The diagnosis of poisoning was based on history of ingestion and characteristic clinical features of anticholinesterase agent poisoning. Prior to treatment, all symptoms recorded at emergency room and blood samples for blood chemistry including plasma amylase and plasma acetyl-cholinesterase were collected from each patient immediately after the admission. RESULTS: As clinical manifestations of OP show, nausea and vomiting and salivation were the leading manifestations, 45.2% and 33.3%, respectively. Patients who developed respiratory failure were older than those who did not(54.3 ± 6.9 vs. 43.1 ± 5.6, p < 0.05). The dosage of atropine administered for treatment was significantly higher in the patient group with respiratory failure compared to those without respiratory failure(29.7 ± 14.5 vs. 9.1 ± 10.2, p < 0.05). Plasma amylase level of the patient group with respiratory failure was significantly higher than those without respiratory failure(436.1 ± 87.1 vs. 181.3 ± 29.6, p < 0.01). Of course, mean days of hospitalization in the respiratory failure group are significantly longer than the other group(12.1 ± 2.1 vs. 5.4 ± 1.9, p < 0.05). Based on univariant analysis, bradycardia, hypotension, fasciculation and coma were significant factors associated with respiratory failure. The dose of atropine administered for treatment was significantly higher in the oral exposure group compared to nonoral exposure group(23.6 ± 12.6 vs. 10.6 ± 6.4, p < 0.05). The same is true for the pralidoxime treatment(9.6 ± 1.9 vs. 5.3 ± 1.4, p < 0.05). As for mean days of hospitalization(11.6 ± 3.9 vs. 6.4 ± 2.1, p < 0.05) and fatality(2 vs. 0, p < 0.05), those of oral exposure patients were significantly longer and higher than those with nonoral exposure. CONCLUSIONS: We demonstrate that elevated plasma amylase concentration was related to the development of respiratory failure in OP intoxication. It also provided us various important risk factors to identify those patients with OP poisoning who would ultimately require ventilatory support. [ABSTRACT FROM AUTHOR]

Background. Approximately 35% of patients acutely poisoned with organophosphates (OP) in developing countries like Sri Lanka require intensive care and mechanical ventilation. However, death rates remain high. OBJECTIVE: To study the outcomes and predictors of mortality in patients with acute OP poisoning requiring intensive therapy at a regional center in Sri Lanka over a period of 40 months. METHODS: Retrospective analysis of all intensive care records of patients with acute OP poisoning admitted to the Intensive Care Unit (ICU) between March 1998 and July 2001. RESULTS: During the study period, 126 subjects were admitted to the ICU with acute OP poisoning. Records of 10 patients were lost and those of 37 were incomplete and hence were excluded. All the remaining 71 patients (59 male) had required endotracheal intubation and mechanical ventilation for a period of four (median) days (range 1–27) in addition to gastric lavage and standard therapy with atropine and oximes and adequate hydration. Of these 71 patients, 36 (28 male) had died. Life table analysis demonstrated a steep decline in the cumulative survival to 67% during the first three days. Systolic blood pressure of < 100 mmHg and FiO2 of > 40% to maintain a SpO2 of > 92% within the first 24 h were recognized as poor prognostic indicators among mechanically ventilated patients. CONCLUSION: Mortality following OP poisoning remains high despite adequate respiratory support, intensive care, and specific therapy with atropine and oximes. One-third of the subjects needing mechanical ventilation and reaching intensive care units die within the first 72 h of poisoning. Systolic blood pressure of less than 100 mmHg and the necessity of a FiO2 > 40% to maintain adequate oxygenation are predictors of poor outcome in patients mechanically ventilated in the ICU. [ABSTRACT FROM AUTHOR]

Current treatment of acute organophosphate (OP) poisoning includes acombined administration of a cholinesterase reactivator (oxime), a muscarinic receptor antagonist (atropine) and an anticonvulsant (diazepam). This treatment is not adequate since it does not prevent neuronal brain damage and incapacitation. Here, as in a recent review it isstated that other therapeutic approaches may improve protection. Former studies on the 'direct effects' of oximes led to the conclusion that drug-induced inhibition of acetylcholine (ACh)-release shortly (1min) after the acute OP-intoxication, could prevent and counteract convulsions and improve survival. In general, the accumulation of ACh in the synaptic cleft is considered to be responsible for the symptoms that ultimately lead to death. Therefore, prevention or suppressionof this excessive accumulation of ACh could be a generic approach toantagonize OP-poisoning. Preliminary evidence for this concept has been put forward. Evaluation of drugs that would be able to prevent and counteract ACh accumulation, led to the conclusion that adenosine receptor agonists could be promising candidates. Pilot experiments demonstrated that intramuscular administration of the adenosine receptoragonists NECA (5'-N-ethylcarboxamido-adenosine) or CPA (N6-cyclopentyl adenosine) 1 min following a subcutaneous soman poisoning (1.5 - 2LD50) in rats, resulted in (1) prevention or postponement of chewing, salivation, convulsive activity, and respirator distress (cholinergic symptoms) (2) improvement of survival rate (24 h). (3) alow level of extracellular brain ACh, as opposed to high levels of extracellular brain ACh in untreated animals. It is concluded that (1)adenosine agonists protect acutely soman-poisoned rats without the need of additional treatment of atropine, oxime or diazepam, (2) prevention of ACh accumulation in this way may be a new generic approach in the treatment of OP-poisoning. [ABSTRACT FROM AUTHOR]