The role of a combination of N-acetylcysteine and magnesium sulfate as adjuvants to standard therapy in acute organophosphate poisoning: A randomized controlled trial.

Background: Mortality in acute organophosphate (OP) poisoning remains high despite current standard therapy with atropine and oximes. Due to dose-limiting side effects of atropine, novel therapies are targeting other putative mechanisms of injury, including oxidative damage, to reduce atropine dosage. Objectives: N-acetylcysteine (NAC) and magnesium sulfate (MgSO4) have different mechanisms of actions and should act synergistically in OP poisoning. In this study, we wanted to evaluate whether this novel combination, used as an adjuvant to standard care, could improve clinical outcomes. Methods: The study was conducted in the Emergency Department and ICU of AIIMS Bhubaneswar (a tertiary care center and government teaching institute) between July 2019 and July 2021. Eighty-eight adult patients with history and clinical features of acute OP poisoning were randomly allocated (1:1) into two groups. The Study group received 600 mg NAC via nasogastric tube thrice daily for 3 days plus a single dose of 4 g Inj. MgSO4 IV on first day and the Control group received suitably matched placebo (double-blinding) - in addition to standard care in both the groups. The primary outcome measure was to compare the total dose of Inj. Atropine required (cumulative over the entire treatment duration) between the control group and the study group receiving NAC and MgSO4. The secondary outcome measures were lengths of ICU and hospital stays, need and duration of mechanical ventilation, the differences in BuChE activity, oxidative stress biomarkers - MDA and GSH levels, the incidences of adverse effects including delayed sequalae like intermediate syndrome and OPIDN, and comparison of mortality between the two groups. Results: Data from 43 patients in Control and 42 patients in Study group was finally analyzed. The baseline parameters were comparable. Total atropine requirements were lower in the Study group [175.33 ± 81.25 mg (150.01-200.65)] compared to the Control [210.63 ± 102.29 mg (179.15-242.11)] [Mean ± SD (95% CI)], but was not statistically significant. No significant differences in any of the other clinical or biochemical parameters were noted. Conclusion: The N-acetylcysteine and MgSO4 combination as adjuvants failed to significantly reduce atropine requirements, ICU/hospital stay, mechanical ventilatory requirements, mortality and did not offer protection against oxidative damage.

Clinical correlates of hypotension in patients with acute organophosphorus poisoning.

BACKGROUND: The aim of the present study is to describe the clinical correlates of hypotension and its associated outcomes in patients with acute organophosphorus poisoning (AOPP). METHODS: In this retrospective cohort study, we analyzed data pertaining to 871 patients with AOPP who were treated at two hospitals. Data from hypotensive and non-hypotensive patients were compared to identify clinical correlates of hypotension. We also evaluated the association between clinical parameters (including hypotension) and in-hospital mortality. RESULTS: The incidence of hypotension in AOPP patients was 16.4%. Hypotensive patients showed significantly higher in-hospital mortality (1.1% vs. 39.9%, P<0.001). Advanced age (odds ratio [OR] 1.25, 95% confidence interval [CI] 1.08-1.44), history of diabetes (OR 2.65, 95% CI 1.14-5.96), and increased white blood cell count (OR 1.06, 95% CI 1.03-1.09), plasma cholinesterase (OR 0.91, 95% CI 0.84-0.94), plasma albumin (OR 0.88, 95% CI 0.85-0.92), serum amylase (OR 1.01, 95% CI 1.01-1.02), and blood pH (OR 0.64, 95% CI 0.54-0.75) were significantly associated with hypotension. After adjusting for potential confounders, hypotension was associated with increased in-hospital mortality (hazard ratio 8.77-37.06, depending on the controlled variables). CONCLUSIONS: Hypotension is a common complication of AOPP and is associated with increased in-hospital mortality. Advanced age, history of diabetes, and changes in laboratory parameters were associated with hypotension in AOPP patients.

Development of a practical prediction scoring system for severe acute organophosphate poisoning.

Acute organophosphorus poisoning (AOPP) is a serious public health issue, especially in the rural areas. This study was designed to establish a scoring system to assess the risk of cases with severe AOPP. A retrospective cohort study was conducted at two independent hospitals. The derivation cohort included 444 patients with AOPP and the validation cohort included 274 patients. A risk score for patients with severe AOPP was developed. The rates of severe AOPP cases were 20.7% and 20.1% in the derivation and validation cohorts, respectively. A scoring system for severe AOPP risk was developed that included: (1) age >50 years, (2) white blood cell count of >15 × 109 /L, (3) plasma cholinesterase of <360 U/L, (4) plasma albumin of <35 g/L, (5) blood pH <7.3, and (6) lactic acid >3.0 mmol/L. The predicted score in severe cases of AOPP had good accuracy in both the derivation (area under the receiver operating characteristic curve [AUC] 0.88, 95% confidence interval [CI], 0.85-0.92) and validation cohorts (AUC 0.83, 95% CI, 0.77-0.90). A practical bedside prediction scoring system was developed for patients with severe AOPP. The routine use of this scoring system could rapidly assist in identifying patients at higher risk who require more intensive care or transfer to a larger better-equipped hospital.

Acute organophosphate poisoning: 17 years of experience of the National Poison Control Center in Serbia.

Based on human toxicity studies, by appropriate regulatory decisions, the number of organophosphates (OP) on Serbian market has reduced significantly over the last two decades, followed by a gradual decrease in the number of poisonings by organophoshates, treated at the National Poison Control Centre (NPCC). METHODOLOGY: The aim of this retrospective study is to present data regarding the clinical management of poisoning with OP pesticides at the NPCC, that we collected during the 17 years period (1998-2014). RESULTS: In the period 1998-2014, about 17.250 patients were hospitalized at the NPCC, there were around 14.000 patients treated for poisoning by various toxic agents, and among them 410 cases (3%) due to poisoning with OP pesticides. In this period, 92% of OPI poisonings treated in the NPCC were suicidal by intention, while only 8% were due to accidental ingestion or inhalation. The most common clinical signs of poisoning in patients exposed to anticholinesterase pesticides, observed at Clinic of Toxicology of the NPCC were miosis (63.4%), bronchorrhoea (51.9%), vomiting and diarrhea (44.8%), hypotension (19.5%). Acute respiratory insufficiency was registered in 81 (19.7%) and acute cardiocirculatory failure in 16 (3.9%) patients. There were about 25% of most severely poisoned patients. Besides general supportive measures (decontamination, respiratory support), specific pharmacological treatment (atropine, oxime, diazepam) was applied. The highest total administered dose of atropine at NPCC was 6400 mg. However, the most patients received total doses of atropine up to 500 mg (32%). CONCLUSION: Acute poisoning with OP pesticides is not frequent in Serbia, however, it represents important clinical feature due to severity, possible complications and their impact on duration and costs of hospitalization. Initial treatment involves prevention of further absorption and provision of supportive care, followed by administration of specific antidotes. According to its role, the National Poison Control Centre in Belgrade, in addition to treatment of acute poisonings, continuously performs toxicovigilance, i.e. the identification, investigation and evaluation of various toxic risks in the community in order to undertake adequate and timely procedures. Permanent efforts are being made in order to reduce availability and to improve control measures for pesticides marketing.

Evaluation of chromosomal DNA damage, cytotoxicity, cytostasis, oxidative DNA damage and their relationship with endocrine hormones in patients with acute organophosphate poisoning.

Pesticides are commonly used compounds in agriculture. Especially, organophosphates (OPs) are among the extensively used pesticides. Therefore, OPs poisoning is common, especially in underdeveloped and developing countries. Primary aim of this study was to research the effects of acute OPs poisoning on genome instability in the individuals' lymphocytes with acute OPs poisoning both by using the cytokinesis-block micronucleus cytome (CBMN-cyt) assay to examine chromosome/genome damage, cell proliferation index and cell death rate and by using the plasma 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels to determine oxidative DNA damage. Secondary aim of this study was also to assess whether a relation exists between endocrine hormones and the genome damage in acute OPs poisoning. In the study, blood samples were analysed of 13 patients before and after treatment admitted to the Department of Intensive Care Unit with acute OPs poisoning and of 13 healthy subjects of similar age and sex. The present study demonstrates that genome damage (micronucleus; MN and nucleoplasmic bridges; NPBs frequencies), apoptotic and necrotic cell frequencies increased in lymphocytes of patients with acute OPs poisoning before treatment and decreased after treatment. The present study also show that CBMN cyt assay parameters and 8-OHdG levels could be affected by some endocrine hormones such as E2, fT3, fT4, GH, IGF-1, FSH, LH, TSH, PRL, but not be related to ACTH and tT levels in acute OPs poisoning. In conclusion, it is believed that this is the first study to evaluate the chromosomal/oxidative DNA damage, cell proliferation, cell death and their associations with endocrine hormones in acute OPs poisoning. These preliminary findings need to be supported by further studies with larger sample sizes.