Multiple Electrolytes Solution Versus Saline as Bolus Fluid for Resuscitation in Pediatric Septic Shock: A Multicenter Randomized Clinical Trial.

OBJECTIVE: To determine if initial fluid resuscitation with balanced crystalloid (e.g., multiple electrolytes solution [MES]) or 0.9% saline adversely affects kidney function in children with septic shock. DESIGN: Parallel-group, blinded multicenter trial. SETTING: PICUs of four tertiary care centers in India from 2017 to 2020. PATIENTS: Children up to 15 years of age with septic shock. METHODS: Children were randomized to receive fluid boluses of either MES (PlasmaLyte A) or 0.9% saline at the time of identification of shock. All children were managed as per standard protocols and monitored until discharge/death. The primary outcome was new and/or progressive acute kidney injury (AKI), at any time within the first 7 days of fluid resuscitation. Key secondary outcomes included hyperchloremia, any adverse event (AE), at 24, 48, and 72 hours, and all-cause ICU mortality. INTERVENTIONS: MES solution ( n = 351) versus 0.9% saline ( n = 357) for bolus fluid resuscitation during the first 7 days. MEASUREMENTS AND MAIN RESULTS: The median age was 5 years (interquartile range, 1.3-9); 302 (43%) were girls. The relative risk (RR) for meeting the criteria for new and/or progressive AKI was 0.62 (95% CI, 0.49-0.80; p < 0.001), favoring the MES (21%) versus the saline (33%) group. The proportions of children with hyperchloremia were lower in the MES versus the saline group at 24, 48, and 72 hours. There was no difference in the ICU mortality (33% in the MES vs 34% in the saline group). There was no difference with regard to infusion-related AEs such as fever, thrombophlebitis, or fluid overload between the groups. CONCLUSIONS: Among children presenting with septic shock, fluid resuscitation with MES (balanced crystalloid) as compared with 0.9% saline resulted in a significantly lower incidence of new and/or progressive AKI during the first 7 days of hospitalization.

Content validation of school readiness module and school readiness scale for assessing school readiness in children with autism spectrum disorder.

BACKGROUND: There is a paucity of research on interventions targeting preschool children with autism spectrum disorders (ASD) for school readiness. OBJECTIVES: The objectives of this study are to develop and validate a school readiness module for making children with ASD ready for inclusive education and a scale to assess school readiness in them. METHODS: Based on literature review, principles of learning, and techniques of behavioral intervention, a module was developed and reviewed by independent experts regarding the utility of the contents. A scale to assess school readiness was also developed to measure the impact of administering the module on children with ASD which was also validated by the same set of experts. Lawshe's content validity ratio was used to assess the appropriateness of each item for inclusion in the module and scale. RESULTS: Experts (n = 6) gave their opinion on the usefulness of the School Readiness module for children with ASD. The experts agreed that most of the content under each component were valid with the exception of identification of objects by function, identification of environmental sounds and answering social questions. Similarly, in the school readiness scale there was good agreement for all items except for 1 item under domain 2 and 2 items under domain 5. CONCLUSION: A school readiness module and a scale to assess school readiness based on interventions provided as per the school readiness module were developed and validated. Further studies are needed to assess the utility of the module and scale in children with ASD.

Methylation Status of VDR Gene and its Association with Vitamin D Status and VDR Gene Expression in Pediatric Tuberculosis Disease.

Deficiency in circulatory vitamin D level and vitamin D receptor DNA methylation could be associated with weakened innate immune response and increased susceptibility to tuberculosis (TB) disease in children. Therefore, we aimed to study the effect of vitamin D receptor (VDR) gene methylation on plasma vitamin D level and the expression of the VDR gene in children with active-TB disease. A cross-sectional comparative study was conducted in 43 children with active-TB and 33 healthy control children (HC). The vitamin D level was measured in plasma, while the levels of VDR gene promoter methylation and VDR gene expression were measured in peripheral blood. Children with active-TB showed a significantly lower median vitamin D level than HC [Cases 17.18 ng/mL (IQR, 8.3-18.6 ng/mL); HC 41.34 ng/mL (IQR, 40.2-43.49 ng/mL) (p<0.0001)] and decreased mRNA expression level of VDR gene [Cases 0.51 (IQR, 0.40-0.70); HC 1.06 (IQR, 0.8-1.2) (p<0.0001)] and increased VDR DNA methylation [Cases 75% (IQR, 50-75%); HC 10% (IQR, 10-25%) (p<0.0001)]. The VDR hypermethylation is significantly associated with reduced vitamin D level and decreased expression level of VDR gene. Therefore this inverse association could be involved in the impairment in the VDR mediated cytolytic and antimicrobial effector cell response in pediatric TB disease.

Assessment of the Endotracheal Tube Tip Position by Bedside Ultrasound in a Pediatric Intensive Care Unit: A Cross-sectional Study.

Introduction: The chest X-ray (CXR) is the standard of practice to assess the tip of the endotracheal tube (ETT) in ventilated children. In many hospitals, it takes hours to get a bedside CXR, and it has radiation exposure. The objective of this study was to find the utility of bedside ultrasound (USG), in assessing the ETT tip position in a Pediatric Intensive Care Unit (PICU). Methods: It was a prospective study conducted in the PICU of a tertiary care center involving 135 children aged from 1 month to 60 months, requiring endotracheal intubation. In this study, the authors compared the position of the ETT tip by the CXR (gold standard) and USG. The CXR was taken in children to assess the correct position of the tip of ETT. The USG was used to measure the distance between the tip of ETT and the arch of the aorta, thrice in the same patient. The mean of the three USG readings was compared with the distance between the tip of the ETT and carina in CXR. Results: The reliability of three USG readings was tested by absolute agreement coefficient in intraclass correlation (ICC), 0.986 (95% CI: 0.981-0.989). The sensitivity and specificity of the USG in identifying the correct position of the ETT tip in children when compared to CXR were 98.10% (95% CI: 93.297-99.71%) and 50.0% (95% CI: 31.30-68.70%), respectively. Conclusion: In ventilated children <60 months of age, identifying the tip of ETTs by bedside the USG has good sensitivity (98.10%) but poor specificity (50.0%). How to cite this article: Subramani S, Parameswaran N, Ananthkrishnan R, Abraham S, Chidambaram M, Rameshkumar R, et al. Assessment of the Endotracheal Tube Tip Position by Bedside Ultrasound in a Pediatric Intensive Care Unit: A Cross-sectional Study. Indian J Crit Care Med 2022;26(11):1218-1224.

Serious Adverse Reactions to Anti-snake Venom in Children with Snake Envenomation: An Underappreciated Contributor to Snakebite Mortality?

BACKGROUND: Deaths due to snakebites and serious adverse reactions to anti-snake venom (ASV) are both underreported in India. Serious adverse reactions to ASV are common, contributing significantly to mortality and morbidity. We conducted a study to determine the frequency of occurrence of severe adverse reactions to ASV in children and study the various risk factors and their outcomes. PATIENTS AND METHODS: We carried out a retrospective record review of all children of snake envenomation admitted in our tertiary care teaching hospital, from January 2013 to December 2016. Children aged 0 to 12 years admitted for snake envenomation and who received ASV as part of their treatment were included. Details about their management, including ASV usage and any adverse effects noted, were collected on a standard data collection form. RESULTS: Sixty-eight children were enrolled. Hemotoxic (52.9%) envenomation was more common than neurotoxic (35.2%). Severe adverse reactions were present in 42.6%, hypotension in 38.2%, and bronchospasm in 4.4% of the children. The overall mortality rate was 16.1%, anaphylaxis to ASV contributing to 36.3% of them. Mortality was significantly higher in cases with severe adverse reactions (p = 0.005). ASV reactions were also significantly different with different manufacturers. CONCLUSIONS: There is a high frequency of occurrence of severe adverse reactions to ASV resulting in significant morbidity and mortality. HOW TO CITE THIS ARTICLE: Hooda R, Parameswaran N, Subramanian M. Serious Adverse Reactions to Anti-snake Venom in Children with Snake Envenomation: An Underappreciated Contributor to Snakebite Mortality? Indian J Crit Care Med 2021;25(6):720-723.

Methylation status of alu repetitive elements in children with tuberculosis disease.

Background: Investigation of DNA methylation in Alu repetitive elements (REs) was shown to be a promising field to explore transcriptional changes in human genome under disease condition. To scrutinize the association between Alu methylation and tuberculosis (TB) disease in children, the difference in Alu DNA methylation level was compared with healthy controls. Methods: Whole-blood genomic DNA from 36 TB-infected children and 32 healthy controls was isolated, and the level of Alu repeat DNA methylation was examined by methylation-specific polymerase chain reaction. Results: The median Alu methylation level in TB patients was 30% (Interquartile range [IQR], 25-30%), whereas in healthy controls, it was 75% (IQR, 50-75%) (P < 0.0001). The median level of DNA methylation of Alu RE in TB cases was significantly lower than healthy controls. Receiver operating characteristic curve analysis showed that the area under the curve for diagnosis was 0.969 (95% confidence interval, 0.936-1) (P < 0.0001), with 100% sensitivity and 84% specificity. Conclusion: Our results point out that detection of Alu DNA methylation in whole-blood DNA may be clinically useful tool for the diagnosis and prognosis of TB disease in children.

Rapid and Accurate Diagnosis of Acute Pyogenic Meningitis Due to Streptococcus Pneumoniae, Haemophilus influenzae Type b and Neisseria meningitidis Using A Multiplex PCR Assay.

INTRODUCTION: Acute bacterial meningitis is one of the major causes of morbidity and mortality in children and geriatric population, especially in developing countries. Methods of identification are standard culture and other phenotypic tests in many resource poor settings. AIM: To use molecular methods for the improvement of aetiological diagnosis of acute pyogenic meningitis in patients. MATERIALS AND METHODS: CSF samples of 125 patients were included for the study. Gram staining and culture were performed according to standard procedures. Antigen was detected using commercial latex agglutination test kit. Multiplex PCR was performed using previously published primers and protocols. Fischer's exact test was used for finding association between presence of the disease and clinical/biochemical parameters, considering two tailed p<0.05 as statistically significant. Sensitivity, specificity, positive and negative predictive values were calculated using Graphpad QuicCalc software. RESULTS: A total of 39 cases (31.2%) were confirmed to be of acute pyogenic meningitis based on biochemical methods. Only 10/39 was positive for the three organisms tested. Multiplex PCR was able to detect one additional isolate each of Streptococcus pneumoniae and Haemophilus influenzae type b. When compared with multiplex PCR as the gold standard, culture and latex agglutination tests had same sensitivity (80%), specificity (100%), PPV (100%) and NPV (97.8%), whereas Gram stain had poor sensitivity (40%) and good specificity (95.6%). Detection rates were higher in multiplex PCR for the two organisms Streptococcus pneumoniae and Haemophilus influenzae type b. CONCLUSION: Multiplex PCR was more sensitive than culture or antigen detection, and employing this assay can significantly increase the speed and accuracy of identification of the pathogen.

Maternal and birth risk factors for children screening positive for autism spectrum disorders on M-CHAT-R.

This study was carried out to screen children aged 16-30 months, attending pediatric outpatient department of JIPMER, Puducherry, during June to August 2014, for ASD using modified checklist for autism in toddlers-revised (MCHAT-R) and to find association between maternal, birth and postnatal risk factors with risk of ASD. A total of 350 mother-child pairs with children aged between 16 and 30 months were recruited. M-CHAT-R was administered to all mothers to screen for ASD along with risk checklist. Based on screen result children were classified as ASD (high risk) and no ASD (low and medium risk) group. The association between risk factors and screen positivity for ASD was studied using odds ratio. According to our study, 33 (9.4%) screened positive for ASD. Mean age was 21 months. High mean paternal age at birth (P value 0.025), need for resuscitation at birth (OR 3.4, 95% CI 1.47-8.10), NICU stay >12h (OR 4.7, 95% CI 2.26-9.94), late initiation of breastfeeding (OR 3.9, 95% CI 1.83-8.39), neonatal seizures (OR 11.8, 95% CI 5.38-26.25) were associated with screen positivity for ASD. After adjusting for confounding, neonatal seizures, and maternal concern about child development were associated with increased odds of screening positive for ASD whereas exclusive breast feeding in the first 6 months of life is associated with decreased odds. Screening for ASD in children with above risk factors might help in early initiation of remedial interventions.

Haemolytic uraemic syndrome associated with Pseudomonas aeruginosa sepsis.

Haemolytic uraemic syndrome (HUS) is a recognized complication of infection with Shiga toxin-producing Escherichia coli (STEC) and Shigella dysenteriae type 1. Infections with other micro-organisms, especially Streptococcus pneumoniae, have been cited as causes of HUS. In addition, influenza virus and other viruses may rarely be associated with this syndrome. A 2-year-old girl presented with severe Pseudomonas aeruginosa sepsis with renal failure and ecthyma gangrenosum. Further investigations revealed features of HUS. She was managed with antibiotics and other supportive measures including peritoneal dialysis, and subsequently made a full recovery. A possible role of neuraminidase in the pathogenesis of P. aeruginosa-associated HUS was proposed. This is the first reported case of P. aeruginosa sepsis leading to HUS.