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

Preoperative C-reactive protein - Albumin ratio as a predictor of requirement for postoperative mechanical ventilation after non-cardiac surgery under general anaesthesia: A prospective observational study (HICARV)

Background and Aims: Mechanical ventilation is an essential but limited resource worldwide. Appropriate perioperative utilisation of such useful resource demands in time prediction where literature does not have enough data. High C-reactive protein (CRP) and low albumin both represent a state of exaggerated inflammation and poor nutrition, the combination of which might represent the sick surgical patients. Therefore, we tried to evaluate the performance of ratio between preoperative CRP and albumin (CAR) for the prediction of postoperative mechanical ventilation. Methods: After approval from the ethics committee and trial registration, the study was carried out over 2 years. It included 580 adults undergoing non-cardiac surgeries under general anaesthesia. Blood samples were collected for estimation of CRP and albumin, and all were followed up for the need of mechanical ventilation in the postoperative period till hospital discharge. Results: Sixty-six of the analysed 569 patients (11.6%) required postoperative mechanical ventilation in whom the median CAR was higher {0.38 (0.10, 1.45)} than those who did not require the same {0.20 (0.07, 0.65)}, although not statistically significant. A ROC curve analysis found that there is a 58% chance that a CAR will distinguish between the patients requiring postoperative mechanical ventilation from those who do not (AUC = 0.58), which is statistically significant (P value = 0.024). Logistic regression did not result in a significant odds of mechanical ventilation with higher ratio {Odds ratio = 1.06 (0.98, 1.16)}. Conclusions: High CRP–albumin ratio was found to be associated with higher need for mechanical ventilation in patients undergoing surgery under general anaesthesia, but failed to predict the need for mechanical ventilation

Diagnostic accuracy of Leucine-rich α-2 glycoprotein (LRG) as a urinary biomarker in pediatric appendicitis: a prospective observational pilot study from Eastern India

Abstract Background Recently, several serum and urinary biomarkers have been investigated for diagnosis of acute appendicitis. Urinary biomarkers seem to be advantageous in children as it is non-invasive, painless, and easy to perform. Leucine-rich α-2-glycoprotein (LRG) is regarded as a reliable urinary biomarker for the diagnosis of pediatric appendicitis. A prospective observational pilot study was conducted in children presenting with abdominal pain. Assessment of pediatric appendicitis score (PAS), routine blood tests, and measurements of urinary LRG was done. The present study aimed to evaluate the diagnostic accuracy of urine LRG in appendicitis in Indian children and to assess the concentration of urine LRG at which it will guide the management. Results LRG had a receiver operating characteristic (ROC) area under the curve (AUC) of 0.586 (95% CI 0.407–0.766). There was no specific cut-off identified using Youden’s index. ROC analysis of the PAS score resulted in an AUC of 0.821 (95% CI 0.691–0.952). Using Youden’s index, the cut-off for PAS scoring was identified as 6.5 with the sensitivity of 80%, the specificity of 76.2%, positive predictive value 76.19%, negative predictive value as 80%, and diagnostic accuracy of 78%. Conclusions LRG could not show better diagnostic performance compared to routine blood tests and PAS scores. There was no specific cut-off value at which it will differentiate mesenteric adenitis and acute appendicitis and guide their management. With 78% diagnostic accuracy, PAS score (> 6) is still a better tool for the diagnosis of acute appendicitis. Trial registration Clinical Trials Registry Government of India,  CTRI/2018/01/011182 , Registered on: 08 Jan 2018

Role of platelets in the pathogenesis of antiphospholipid syndrome

Aim: To delineate the role of platelets in thrombotic process in APS patients. Background: Pathogenesis of APS is an ongoing area of research and studying the role of platelets will be helpful in developing newer diagnostic and therapeutic strategies. Materials and methods: Forty patients with APS, diagnosed as per modified 2006 Sapporo’s Criteria and who were not on aspirin or any other antiplatelet drug, were included. The same number of age- and sex-matched healthy controls was also recruited for comparison. The following platelet function studies were performed using the blood samples collected from APS patients as well as healthy controls: platelet aggregation studies, platelet secretion of dense granules (a. total degranulation b. platelet secretion of granules in relation to time c. visualization of platelet degranulation), clot retraction studies, and western blot studies on clot retracted samples for demonstration of activated proteomes. Results: A significant increase (P < 0.001) in the platelet aggregation in APS patients as compared to healthy controls was noted. The subjects also showed a significant increase (P < 0.05) in the platelet granule release as well as more degranulation (P < 0.001) in relation to time at stored condition, which were well-visualized under phase-contrast microscope. Sixty-five percent of APS patients showed lesser as well as delayed clot retraction as compared to healthy controls, signifying that the platelet clots are less retractile in APS patients. Conclusion: The study clearly demonstrates the hyperactivity of platelets in APS patients in each step of their activation as compared to the controls. This indicates the major role played by platelets in APS pathogenesis