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Caspases as prognostic markers and mortality predictors in acute organophosphorus poisoning.

ABSTRACT: BACKGROUND:Organophosphorus (OP) compounds have been widely available for decades in agriculture for crop protection and as cheap pest controllers, which increases the rate of exposure and poisoning cases. Using serum cholinesterase as prognostic markers for the acute OP toxicity is controversial; therefore, we aim to find out prognostic biomarkers that best correlate with mortality and outcomes of patients with acute OP toxicity. Levels of serum oxidative stress biomarkers (malondialdehyde (MDA) and total antioxidant capacity (TAC)) and activity of the apoptotic biomarkers (caspase 3 and caspase 9) and pseudo-cholinesterase (p.ChE) were performed. Also, we evaluated the apoptotic capacity through determining the genotoxic effects and chromosomal abnormalities among OP intoxicated patients. RESULTS:We found the activity of caspases and serum MDA and TAC were significantly increased after OP poisoning and decreased after the appropriate atropine and oxime treatment course. The ROC curve suggested caspases as mortality and outcome predictive markers for acute OP poisoning patients. However, OP poisoning cases before treatment showed significant DNA damage, and they did not show any chromosomal aberration. CONCLUSION:The mentioned results strongly suggest apoptotic-related markers (caspase 3, caspase 9) as prognostic markers for evaluation of the treatment, outcomes, and mortality rate in the acute OP toxicity patients.

SUBMITTER: Tallat S

PROVIDER: S-EPMC7152583 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Caspases as prognostic markers and mortality predictors in acute organophosphorus poisoning.

Tallat Shimaa S Hussien Rania R Mohamed Rania Hassan RH Abd El Wahab Mahmoud B MB Mahmoud Magdy M

Journal, genetic engineering & biotechnology 20200413 1

<h4>Background</h4>Organophosphorus (OP) compounds have been widely available for decades in agriculture for crop protection and as cheap pest controllers, which increases the rate of exposure and poisoning cases. Using serum cholinesterase as prognostic markers for the acute OP toxicity is controversial; therefore, we aim to find out prognostic biomarkers that best correlate with mortality and outcomes of patients with acute OP toxicity. Levels of serum oxidative stress biomarkers (malondialdeh ...[more]

PMID: 32281011

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Project description:BackgroundPoisoning with organophosphorus (OP) insecticides is a major global public health problem, causing an estimated 200,000 deaths each year. Although the World Health Organization recommends use of pralidoxime, this antidote's effectiveness remains unclear. We aimed to determine whether the addition of pralidoxime chloride to atropine and supportive care offers benefit.Methods and findingsWe performed a double-blind randomised placebo-controlled trial of pralidoxime chloride (2 g loading dose over 20 min, followed by a constant infusion of 0.5 g/h for up to 7 d) versus saline in patients with organophosphorus insecticide self-poisoning. Mortality was the primary outcome; secondary outcomes included intubation, duration of intubation, and time to death. We measured baseline markers of exposure and pharmacodynamic markers of response to aid interpretation of clinical outcomes. Two hundred thirty-five patients were randomised to receive pralidoxime (121) or saline placebo (114). Pralidoxime produced substantial and moderate red cell acetylcholinesterase reactivation in patients poisoned by diethyl and dimethyl compounds, respectively. Mortality was nonsignificantly higher in patients receiving pralidoxime: 30/121 (24.8%) receiving pralidoxime died, compared with 18/114 (15.8%) receiving placebo (adjusted hazard ratio [HR] 1.69, 95% confidence interval [CI] 0.88-3.26, p = 0.12). Incorporating the baseline amount of acetylcholinesterase already aged and plasma OP concentration into the analysis increased the HR for patients receiving pralidoxime compared to placebo, further decreasing the likelihood that pralidoxime is beneficial. The need for intubation was similar in both groups (pralidoxime 26/121 [21.5%], placebo 24/114 [21.1%], adjusted HR 1.27 [95% CI 0.71-2.29]). To reduce confounding due to ingestion of different insecticides, we further analysed patients with confirmed chlorpyrifos or dimethoate poisoning alone, finding no evidence of benefit.ConclusionsDespite clear reactivation of red cell acetylcholinesterase in diethyl organophosphorus pesticide poisoned patients, we found no evidence that this regimen improves survival or reduces need for intubation in patients with organophosphorus insecticide poisoning. The reason for this failure to benefit patients was not apparent. Further studies of different dose regimens or different oximes are required.

Project description:BACKGROUND:Acute organophosphorus (OP) poisoning is one of the major causes of mortality among patients presenting to emergency departments in developing countries. Although various predictors of mortality among OP poisoning patients have been identified, the role of repeated measurements of vital signs in determining the risk of mortality is not yet clear. Therefore, the present study examined the relationship between trajectories of vital signs and mortality among OP poisoning patients using latent class growth analysis (LCGA). METHODS:This was a retrospective cohort study using data for 449 OP poisoning patients admitted to Civil-Hospital Karachi from Aug'10 to Sep'16. Demographic data and vital signs, including body temperature, blood pressure, heart rate, respiratory rate, and partial-oxygen pressure, were retrieved from medical records. The trajectories of vital signs were formed using LCGA, and these trajectories were applied as independent variables to determine the risk of mortality using Cox-proportional hazards models. P-values of <?0.05 were considered statistically significant. RESULTS:Data for 449 patients, with a mean age of 25.4?years (range 13-85?years), were included. Overall mortality was 13.4%(n?=?60). In trajectory analysis, a low-declining systolic blood pressure, high-declining heart rate trajectory, high-remitting respiratory rate trajectory and normal-remitting partial-oxygen pressure trajectory resulted in the greatest mortality, i.e. 38.9,40.0,50.0, and 60.0%, respectively, compared with other trajectories of the same parameters. Based on multivariable analysis, patients with low-declining systolic blood pressure were three times [HR:3.0,95%CI:1.2-7.1] more likely to die compared with those who had a normal-stable systolic blood pressure. Moreover, patients with a high-declining heart rate were three times [HR:3.0,95%CI:1.5-6.2] more likely to die compared with those who had a high-stable heart rate. Patients with a high-remitting respiratory rate were six times [HR:5.7,95%CI:1.3-23.8] more likely to die than those with a high-stable respiratory rate. Patients with normal-remitting partial oxygen pressure were five times [HR:4.7,95%CI:1.4-15.1] more likely to die compared with those who had a normal-stable partial-oxygen pressure. CONCLUSION:The trajectories of systolic blood pressure, heart rate, respiratory rate and partial-oxygen pressure were significantly associated with an increased risk of mortality among OP poisoning patients.

Project description:BackgroundDespite the apparent benefits of organophosphate compounds (OPCs) acute organophosphate (OP) pesticide poison is an increasing problem worldwide. In a country like Ethiopia, where agriculture is a major component of the economy, these compounds are readily available to the general public. There is paucity of evidence from Ethiopia showing the pattern of organophosphate poisoning (OPP) in healthcare facilities. The objective of this study was to evaluate retrospectively the pattern of acute OPP at the University of Gondar Teaching Hospital in northwest Ethiopia, during September 2010 through December 2014 was conducted. Data was collected through chart review of patients who were admitted due to poisoning. Data was analysed using SPSS 20.ResultsOrganophosphate poisoning in University of Gondar teaching hospital accounts for about 38.46% of all emergency room admissions for poisoning. Out of the 90 cases studied 60% (54) were women, with male to female ratio of 1:1.5. The mean age of the patients was 25.5 with a standard deviation of 9.45. 56.7% of the cases studies lived in an urban environment compared to 43.3% who lived rurally. In the vast majority of patients, 90% (81) patients had ingested OP as an act of suicide. Regarding the route of exposure, oral ingestion was most common in suicidal cases (88.9%). The elapsed time between the time of poison ingestion and the start of the treatment, ranged from 13 min to 1 day. Health care professionals' useds decontamination methods such as gastric lavage and activated charcoal (45.6%) and 36.7% use atropine for OPP treatment. The mean hospital stay was 0.74 days. In the present study family problems were a leading cause of suicides and accounted for 45.8% of all cases.ConclusionAs a developing nation who economy relies heavily on agriculture, Ethiopia continues to have OP compounds remain a common cause of acute poisonings. This is particularly concerning for younger generation who have high rates of OPP and whose numbers continue to raise. This data suggests that it is essential to strengthen Ethiopians regulatory policy concerning the availability of OPCs. Additionally, it will be important to design an appropriate health education program for the prevention of both suicidal and accidental OPPs for the benefit of the public at large.

Project description:BackgroundA prediction model of mortality for patients with acute poisoning has to consider both poisoning-related characteristics and patients' physiological conditions; moreover, it must be applicable to patients of all ages. This study aimed to develop a scoring system for predicting in-hospital mortality of patients with acute poisoning at the emergency department (ED).MethodsThis was a retrospective analysis of the Injury Surveillance Cohort generated by the Korea Center for Disease Control and Prevention (KCDC) during 2011-2018. We developed the new-Poisoning Mortality Scoring system (new-PMS) to generate a prediction model using the derivation group (2011-2017 KCDC cohort). Points were computed for categories of each variable. The sum of these points was the new-PMS. The validation group (2018 KCDC cohort) was subjected to external temporal validation. The performance of new-PMS in predicting mortality was evaluated using area under the receiver operating characteristic curve (AUROC) for both the groups.ResultsOf 57,326 poisoning cases, 42,568 were selected. Of these, 34,352 (80.7%) and 8216 (19.3%) were enrolled in the derivation and validation groups, respectively. The new-PMS was the sum of the points for each category of 10 predictors. The possible range of the new-PMS was 0-137 points. Hosmer-Lemeshow goodness-of-fit test showed adequate calibration for the new-PMS with p values of 0.093 and 0.768 in the derivation and validation groups, respectively. AUROCs of the new-PMS were 0.941 (95% CI 0.934-0.949, p < 0.001) and 0.946 (95% CI 0.929-0.964, p < 0.001) in the derivation and validation groups, respectively. The sensitivity, specificity, and accuracy of the new-PMS (cutoff value: 49 points) were 86.4%, 87.2%, and 87.2% and 85.9%, 89.5%, and 89.4% in the derivation and validation groups, respectively.ConclusionsWe developed a new-PMS system based on demographic, poisoning-related variables, and vital signs observed among patients at the ED. The new-PMS showed good performance for predicting in-hospital mortality in both the derivation and validation groups. The probability of death increased according to the increase in the new-PMS. The new-PMS accurately predicted the probability of death for patients with acute poisoning. This could contribute to clinical decision making for patients with acute poisoning at the ED.

Project description:BackgroundParaquat is a widely used nonselective and fast-acting contact herbicide worldwide. This study identified the early predictor of mortality in patients with acute paraquat poisoning.MethodsTwenty-nine patients with acute paraquat poisoning admitted at Nanjing Drum Tower Hospital from January 2018 to August 2020 were included in this study. The early predictor of mortality in patients with acute paraquat poisoning based on the blood tests was identified by correlation, logistic regression, and receiver operating characteristic (ROC) analyses.Result15 of the 29 patients died after poisoning. Compared to the survivors, the neutrophilic granulocyte ratio, leukocyte count, ALB, and Crea of the nonsurvivors were significantly higher with p value < 0.05, while the lymphocyte ratio and eGFR(MDRD) of the nonsurvivors were remarkably lower with p value < 0.01. Moreover, the neutrophil-to-lymphocyte ratio (NLR) was remarkably upregulated in the nonsurvivors. The area under the ROC curve (AUC) of the neutrophilic granulocyte ratio, lymphocyte ratio, leukocyte count, ALB, Crea, eGFR(MDRD), and NLR to predict the mortality in patients with acute paraquat poisoning was 0.8905 (95% CI: 0.7589-1.022), 0.8643 (95% CI: 0.7244-1.004), 0.8500 (95% CI: 0.7133-0.9867), 0.7286 (95% CI: 0.5338-0.9233), 0.8167 (95% CI: 0.6620-0.9713), 0.8714 (95% CI: 0.7330-1.010), and 0.8667 (95% CI: 0.7277-1.006), respectively. More interestingly, we also evaluated the diagnostic values of the different combinations of six blood test biomarkers by logistic regression analysis. According to the results of the logistic regression analysis, the AUCs for the combination of the neutrophilic granulocyte ratio, leukocyte count, and eGFR(MDRD) were the largest with 0.986 (95% CI: 0.952-1), and the sensitivity and specificity were 100% and 100%.ConclusionThis study demonstrated that the combination of the neutrophilic granulocyte ratio, leukocyte count, and eGFR(MDRD) could serve as an ideal early predictor of mortality in patients with acute paraquat poisoning. However, further research is needed to draw a clear conclusion.

Dataset Information

Caspases as prognostic markers and mortality predictors in acute organophosphorus poisoning.

Publications

Caspases as prognostic markers and mortality predictors in acute organophosphorus poisoning.

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