Severity and Cardiac Involvement in Multisystem Inflammatory Syndrome in Children.

Multisystem inflammatory syndrome in children (MIS-C) occurs secondary to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A retrospective study, involving 6 tertiary-care centers in Haryana, was conducted to evaluate the clinical features, severity, laboratory findings, and outcomes of patients with MIS-C. Disease severity was graded (mild/moderate/severe) and presence of cardiac abnormalities noted. Patients with and without cardiac abnormalities and with and without severe disease were compared. Forty-eight children with MIS-C were included (median age - 9.5 y). Fever (100%), gastrointestinal (83.3%) and mucocutaneous (50%) symptoms were common. Only 16.7% patients had previous history of documented SARS-CoV-2 infection/contact. Severe disease and cardiac abnormalities were seen in 47.9% and 54.2% patients, respectively. NT-proBNP > 1286.5 pg/mL and thrombocytopenia (≤ 119500/µL) were significant risk factors for severe MIS-C. Forty-five patients (93.8%) recovered and 3 died. Median hospitalization duration was 7 d (5-9.5). MIS-C must be considered as a possibility in any febrile child, even if a positive epidemiological history is absent. High NT-proBNP and thrombocytopenia are significant risk factors for severe MIS-C. (Trial Registration: The study was registered with the Clinical Trials Registry, India (CTRI/2021/09/036491)).

Clinical Features Associated With Need for Mechanical Ventilation in Children With Guillain-Barré Syndrome: Retrospective Cohort From India.

OBJECTIVES: To analyze the clinical features associated with the need for mechanical ventilation (MV) in children with Guillain-Barré syndrome (GBS). DESIGN: Retrospective cohort study, 2010-2019. SETTING: PICU. PATIENTS: All children, 1 month to 12 years old, diagnosed with GBS in our single-center PICU. INTERVENTION: Retrospective chart and data review. MEASUREMENTS AND MAIN RESULTS: Out of 189 children identified with a diagnosis of GBS, 130 were boys (69%). The median (interquartile range [IQR]) age was 6 years (3-9 yr). At admission, the Hughes disability score was 5 (4-5), and cranial nerve palsies were present in 81 children (42%). Autonomic instability subsequently occurred in a total of 97 children (51%). In the 159 children with nerve conduction studies, the axonal variant of GBS (102/159; 64%) predominated, followed by the demyelinating variant (38/189; 24%). All children received IV immunoglobulins as first-line therapy at the time of admission. The median (IQR) length of PICU stay was 12 days (3-30.5 d). Ninety-nine children (52%) underwent invasive MV, and median duration of MV was 25 days (19-37 d). At admission, upper limb power less than or equal to 3 (p = 0.037; odds ratio (OR), 3.5 [1.1-11.5]), lower limb power less than or equal to 2 (p = 0.008; OR, 3.5 [1.4-8.9]), and cranial nerve palsy (p = 0.001; OR, 3.2 [1.6-6.1]) were associated with subsequent need for MV. Prolonged (> 21 d) MV was associated with more severe examination findings at admission: upper limb power less than or equal to 2 (p < 0.0001; OR, 4.2 [2.5-6.9]) and lower limb power less than or equal to 1 (p < 0.0001; OR, 4.5 [2.6-7.9]). CONCLUSIONS: In children with GBS, referred to our center in North India, severe neuromuscular weakness at admission was associated with the need for MV. Furthermore, greater severity of this examination was associated with need for prolonged (> 21 d) MV. Identification of these signs may help in prioritizing critical care needs and early PICU transfer.

Risk Factors for Cerebral Edema and Acute Kidney Injury in Children with Diabetic Ketoacidosis.

OBJECTIVES: To study the clinical profile and risk factors of cerebral edema and acute kidney injury in children with diabetic ketoacidosis. DESIGN: Retrospective review of medical records. PATIENTS: Fifty consecutive patients (age <18 years) admitted to our pediatric intensive care unit with a diagnosis of diabetic ketoacidosis over 5 years. MATERIALS AND METHODS: Retrospective analysis of medical records was done, and data including patients' age, sex, presenting features, biochemical profile including blood glucose, osmolality, urea, creatinine, and venous blood gas, electrolytes were recorded at admission, at 12 and 24 hours. Treatment details including fluid administration, rate of fall of glucose, time to resolution of diabetic ketoacidosis were noted. Complications such as cerebral edema and acute kidney injury were recorded. Patients with and without cerebral edema and acute kidney injury were compared. Variables that were significant on univariate analysis were entered in a multiple logistic regression analysis to determine the independent predictors for cerebral edema and acute kidney injury. Odds ratio and 95% confidence interval were calculated using SPSS version 22. MEASUREMENTS AND MAIN RESULTS: Between November 2015 and 2020, 48 patients were admitted for a total of 50 episodes of diabetic ketoacidosis. Two patients had recurrent diabetic ketoacidosis. Median age was 9.5 years (range 1-17). Thirty-one patients (62%) had new-onset type I diabetes mellitus. Twenty-two patients (44%) presented with severe diabetic ketoacidosis. Cerebral edema and acute kidney injury were seen in 11 (22%) and 15 (30%) patients, respectively. On multiple logistic regression analysis, higher blood urea level, lower serum bicarbonate level, and higher corrected sodium levels at admission were identified to be variables independently associated with risk of cerebral edema. CONCLUSIONS: Higher corrected sodium, higher urea level, and lower serum bicarbonate levels at admission are predictive of cerebral edema in patients presenting with diabetic ketoacidosis. The severity of dehydration and acidosis in DKA appears to be a common factor responsible for the development of dysfunction of both brain and kidney. HOW TO CITE THIS ARTICLE: Raghunathan V, Jevalikar G, Dhaliwal M, Singh D, Sethi SK, Kaur P, et al. Risk Factors for Cerebral Edema and Acute Kidney Injury in Children with Diabetic Ketoacidosis. Indian J Crit Care Med 2021;25(12):1446-1451.

Liquid Mosquito Repellent Ingestion in Children.

OBJECTIVES: Hydrocarbons are a common cause of accidental poisoning in children, with kerosene being the most implicated agent in rural parts of India. However, lately, liquid mosquito repellent ingestion is emerging as an important cause of hydrocarbon (kerosene) poisoning in urban households. METHODS: This is a retrospective case series over a 5-y period (January 2013 - December 2017) of children with accidental liquid mosquito repellent ingestion presenting to the pediatric emergency. Epidemiology, clinical profile, management and outcomes are discussed. RESULTS: Twenty-three children with median (IQR) age of 24 (18.8-32) mo presented after mean (SD) interval of 6 (3) h from ingestion. Majority (20, 87%) were seen during summer months (March-June) and all were from urban background. Sixteen (70%) had mild-moderate acute respiratory distress syndrome (ARDS) requiring supplemental oxygen with or without positive airway pressure for a mean (SD) duration of 3.3 (1.9) d. All except one survived. CONCLUSIONS: Children with accidental liquid mosquito repellent ingestion had predominant aspiration pneumonitis due to hydrocarbon content rather than neurological complications attributable to synthetic pyrethroids. Ensuring child-proof containers, appropriate storage, regulatory surveillance and parental awareness are must for prevention.

Pyogenic Meningitis Complicated with Extensive Central Nervous System Vasculitis and Moyamoya Vasculopathy.

Meningitis is an uncommon complications of head trauma. Vasculitis in bacterial meningitis is seen in 9%-25% of adults. Neurological deficits in bacterial meningitis are seen in about one-third of children. Isolated cranial nerve palsies are common, whereas major deficits such as hemiparesis and quadriparesis are rare. We describe a case of a 7-year-old boy who had post-traumatic meningitis complicated with quadriparesis and severe vasculitis of bilateral anterior and posterior circulation with moyamoya vasculopathy.

Pulmonary Functions in Children Ventilated for Acute Hypoxemic Respiratory Failure.

OBJECTIVE: To assess pulmonary functions of children who received mechanical ventilation for acute hypoxemic respiratory failure. DESIGN: Longitudinal study. SETTING: PICU and Pediatric Pulmonology Clinic of a tertiary care teaching hospital in North India. PATIENTS: All children, 5-12 years old, ventilated for acute hypoxemic respiratory failure in PICU from July 2012 to June 2013 and survived. INTERVENTIONS: The baseline admission variables recorded were as follows: age, sex, duration of illness, primary diagnosis at admission, Pediatric Risk of Mortality III score, lung injury score, mechanical ventilation parameters, oxygenation indices, and duration of PICU stay. The children were followed up twice, at 3 and 9-12 months, after discharge from PICU and evaluated for any residual respiratory symptoms and signs, pulse oximetry, chest radiograph, 6-minute walk test, peak expiratory flow rate, and spirometry. Age, sex, duration of illness, primary diagnosis, Pediatric Risk of Mortality III score, lung injury score, mechanical ventilation parameters, oxygenation indices (PaO2/FIO2 ratio and oxygenation index), and duration of PICU stay were recorded from patient records. MEASUREMENTS AND MAIN RESULTS: Twenty-nine children (25 boys and four girls; mean [SD] age, 8.4 [2.4] yr) were followed up at 3.5 (± 1.2) and 10.6 (± 2.7) months after discharge from PICU. Recurrent respiratory symptoms were noted in 37.9% patients (11/29) during first and in none during second follow-up. None had limitation of physical activity or need of supplemental oxygen. Chest examination was normal in all, except one during first follow-up, but 13.8% (4/29) had abnormal chest radiograph during first follow-up. Nearly all children could perform 6-minute walk test although mean distance walked increased significantly from first (352 ± 66.7 m) to second follow-up (401 ± 60.7 m; p = 0.002). Abnormal spirometry was seen in 82.7% (24/29) versus 18.5% (5/27) children during first and second follow-up visits, respectively (p = 0.0001). Most cases had restrictive abnormality (58.6% vs 11.1%; p = 0.002) during first and second follow-up, respectively. There was no correlation between pulmonary functions and lung injury scores, oxygenation indices (PaO2/FIO2 ratio and oxygenation index), and mechanical ventilation parameters. CONCLUSIONS: Significant number of children ventilated for acute hypoxemic respiratory failure had subclinical pulmonary function abnormality, without limiting physical activity, which improved over time. Further research on this topic with a larger sample size and patient categorization according to recent pediatric acute respiratory distress syndrome definition is needed.

Development of Visually Improved Loop Mediated Isothermal Amplification for the Diagnosis of Plasmodium vivax Malaria in a Tertiary Hospital in Chandigarh, North India.

More than 80% of the global burden of the Plasmodium vivax is contributed by mainly three countries (India, Indonesia, and Pakistan). Reports from last decades have highlighted the occurrence of severe P. vivax malaria which was earlier considered to be benign. The recent trends of increasing P. vivax-associated morbidity and mortality emphasizes the need for early and accurate diagnosis of P. vivax malaria for the timely management of patients. Microscopy is considered a gold standard but needs experienced laboratory technologists. Over the last few years, Polymerase chain reaction (PCR) is being used as a highly sensitive and specific test but it requires expensive equipment which limits its use in the field. Therefore, in the present study, utility of visually improved loop-mediated isothermal amplification (LAMP) for the detection of P. vivax was evaluated targeting 18SrRNA gene in 145 microscopically confirmed P. vivax and 20 P. vivax negative patients. Sensitivity and specificity of LAMP was assessed with respect to microscopy and multiplex nested PCR (nPCR). Results of the LAMP assay was also correlated with rapid diagnostic test, multiplex nPCR and real-time PCR results. Overall, sensitivity and specificity of P. vivax-specific LAMP compared with microscopy were found to be 100% and 85%, respectively. Furthermore, detection limit for LAMP was found to be 0.8 copies/µL and it was also able to detect three complicated cases of P. vivax which were missed by microscopy. This study showed a LAMP assay to be a rapid and very sensitive method for the early diagnosis of both complicated and uncomplicated P. vivax malaria.

Clinical Utility of MRI Brain in Children with Non-traumatic Coma.

OBJECTIVES: To determine characteristics that help identify children with acute encephalopathy who benefit from an MRI (magnetic resonance imaging) of the brain. The secondary objective was to determine the adverse events associated with the MRI procedure. METHODS: In this single center, prospective, observational study. Children (2 mo - 12 y) presenting with impaired consciousness were screened. Those with acute non-traumatic encephalopathy (Glasgow Coma Score of 12 or less) undergoing their first in-patient MRI brain were included. The decision regarding MRI brain was taken by the treating unit. The clinician taking care of the child was requested to categorize the information obtained from MRI into one of the following categories (as per definition): Contributory MRI [Diagnostic and/or Therapeutic, Suggestive or Additive and/or Prognostic (as per definitions)] OR Non-contributory MRI (If results of the MRI did not alter the management of the child in any manner). RESULTS: During the study period, 16,667 children presented to the pediatric emergency, of which 496 children were admitted with a diagnosis of acute encephalopathy and100 children were enrolled for this study. Ninety-two children had a febrile encephalopathy. Seventy-seven (77%, 95% CI 69-85%) children had an MRI that was contributory. In 64(78%) out of 82 children who underwent both CT and MRI, the MRI showed additional findings. Those with abnormal CT were significantly more likely to have a contributory MRI (65.6% vs. 22.2%, P = 0.001). There were 18 adverse events during the MRI procedure. CONCLUSIONS: MRI contributes in management decisions in over three-fourth of children presenting with non-traumatic coma and should be the neuroimaging of choice in acute non-traumatic coma. There are no pre-MRI clues to identify which child is likely to benefit from the MRI. However, if CT detects an abnormality, MRI is likely to significantly add to the information, contributing directly to the management.

Clinical profile and neurodevelopmental outcome of new-onset acute symptomatic seizures in children.

PURPOSE: To study clinical profile, neurodevelopmental outcome and its predictors in children with acute symptomatic seizures (ASS). METHODS: Short-term neurodevelopmental outcome and predictors of poor outcomes were prospectively assessed in 105 consecutive children with ASS aged 3 months-12 years RESULTS: Mean age was 51.2+42.2months (3-144 months); 67.2% were males. Central nervous system (CNS) infection in 82%, status epilepticus in 15.2%, abnormal neuroimaging in 62.8% and abnormal electroencephalography in 22.3% were noted. At discharge, 27.6% had poor outcome including death (13%); CNS infections were significantly associated with poor outcome compared to ASS of other aetiologies (32.6% vs 5.2%, p=0.02). Low GCS (OR 4.9, 95%CI 1.2-20.7), abnormal electroencephalograph (OR 4.3, 95%CI 1-16.9) and neuroimaging (OR 12.1, 95%CI 1.4-105.2) were independent predictors of poor outcome. After 6 months, 16% children had delayed neurodevelopment and cognition; 6% had seizure recurrences. Abnormal electroencephalograph (p=0.002; OR 6.8, 95%CI 2.0-23.1), abnormal neuroimaging (p=0.015; OR 9.47, 95%CI 1.18-75.8),>1 anti-epileptic (p=0.00; OR 9.9, 95%CI 2.88-33.9), intubation (p=0.004; OR 6.25, 95%CI 1.79-21.7) and poor outcome at discharge (p=0.02; OR 4.44, 95%CI1.38-14.2) predicted abnormal neurodevelopment. CONCLUSIONS: CNS infections are the most common cause of ASS in children from developing countries. Abnormal neurodevelopment and seizure recurrences on short-term follow-up are seen in a minority of children.

Sulfonylurea Poisoning in a Healthy Toddler.

Ingestion of sulfonylureas is life-threatening in toddlers and children due to its strong and prolonged hypoglycemic effect. The authors present a 15-mo-old boy with accidental ingestion of Glipizide who presented with encephalopathy, seizure and severe hypoglycemia. The management included parenteral dextrose and octreotide administration to maintain euglycemia, followed by complete neurological recovery within 24 h. Sulphonylurea intoxication should be considered in previously healthy toddlers and children presenting with hypoglycemia especially if any caregiver is on sulfonylurea drugs.

Probiotics in critically ill children.

Gut microflora contribute greatly to immune and nutritive functions and act as a physical barrier against pathogenic organisms across the gut mucosa. Critical illness disrupts the balance between host and gut microflora, facilitating colonization, overgrowth, and translocation of pathogens and microbial products across intestinal mucosal barrier and causing systemic inflammatory response syndrome and sepsis. Commonly used probiotics, which have been developed from organisms that form gut microbiota, singly or in combination, can restore gut microflora and offer the benefits similar to those offered by normal gut flora, namely immune enhancement, improved barrier function of the gastrointestinal tract (GIT), and prevention of bacterial translocation. Enteral supplementation of probiotic strains containing either Lactobacillus alone or in combination with Bifidobacterium reduced the incidence and severity of necrotizing enterocolitis and all-cause mortality in preterm infants. Orally administered Lactobacillus casei subspecies rhamnosus, Lactobacillus reuteri, and Lactobacillus rhamnosus were effective in the prevention of late-onset sepsis and GIT colonization by Candida in preterm very low birth weight infants. In critically ill children, probiotics are effective in the prevention and treatment of antibiotic-associated diarrhea. Oral administration of a mix of probiotics for 1 week to children on broad-spectrum antibiotics in a pediatric intensive care unit decreased GIT colonization by Candida, led to a 50% reduction in candiduria, and showed a trend toward decreased incidence of candidemia. However, routine use of probiotics cannot be supported on the basis of current scientific evidence. Safety of probiotics is also a concern; rarely, probiotics may cause bacteremia, fungemia, and sepsis in immunocompromised critically ill children. More studies are needed to answer questions on the effectiveness of a mix versus single-strain probiotics, optimum dosage regimens and duration of treatment, cost effectiveness, and risk-benefit potential for the prevention and treatment of various critical illnesses.

Survival and neurological outcome following in-hospital paediatric cardiopulmonary resuscitation in North India.

BACKGROUND: Data on outcome of children undergoing in-hospital cardiopulmonary resuscitation (CPR) in low- and middle-income countries are scarce. AIMS: To describe the clinical profile and outcome of children undergoing in-hospital CPR. METHODS: This prospective observational study was undertaken in the Advanced Pediatric Center, PGIMER, Chandigarh. All patients aged 1 month to 12 years who underwent in-hospital CPR between July 2010 and March 2011 were included. Data were recorded using the 'Utstein style'. Outcome variables included 'sustained return of spontaneous circulation' (ROSC), survival at discharge and neurological outcome at 1 year. RESULTS: The incidence of in-hospital CPR in all hospital admissions (n = 4654) was 6.7% (n = 314). 64.6% (n = 203) achieved ROSC, 14% (n = 44) survived to hospital discharge and 11.1% (n = 35) survived at 1 year. Three-quarters of survivors had a good neurological outcome at 1-year follow-up. Sixty per cent of patients were malnourished. The Median Pediatric Risk of Mortality-III (PRISM-III) score was 16 (IQR 9-25). Sepsis (71%), respiratory (39.5%) and neurological (31.5%) illness were the most common diagnoses. The most common initial arrhythmia was bradycardia (52.2%). On multivariate logistic regression, duration of CPR, diagnosis of sepsis and requirement for vasoactive support prior to arrest were independent predictors of decreased hospital survival. CONCLUSIONS: The requirement for in-hospital CPR is common in PGIMER. ROSC was achieved in two-thirds of children, but mortality was higher than in high-income countries because of delayed presentation, malnutrition and severity of illness. CPR >15 min was associated with death. Survivors had good long-term neurological outcome, demonstrating the value of timely CPR.

High-dose Oral Ambroxol for Early Treatment of Pulmonary Acute Respiratory Distress Syndrome: an Exploratory, Randomized, Controlled Pilot Trial.

OBJECTIVE: To evaluate efficacy of high-dose oral ambroxol in acute respiratory distress syndrome (ARDS) with respect to ventilator-free days (VFD). DESIGN: Prospective, randomized, placebo-controlled, blinded pilot trial. PATIENTS: Sixty-six mechanically ventilated patients (1 month to 12 years) with ARDS who were hand-ventilated for <24 hr before pediatric intensive care unit admission. INTERVENTIONS: Patients randomized to oral ambroxol (40 mg/kg/day, in four divided doses) (n = 32) or placebo (n = 34) until 10 days, extubation or death whichever is earlier. MEASUREMENTS AND MAIN RESULTS: Majority (91%) had pneumonia and bronchiolitis. Two study groups were similar in baseline characteristics. Mean partial pressure of arterial oxygen/fraction of inspired oxygen and oxygenation index were >175 and <10, respectively, with no difference in the two study groups. VFD were similar in the two study groups. Overall mortality was 26%. No adverse events were noted with ambroxol. CONCLUSIONS: Among ventilated pulmonary ARDS patients with oxygenation index of <10, mortality was 26%. Ambroxol did not improve VFD. Study with higher and more frequently administered doses of ambroxol in larger sample is suggested after having generated relevant pharmacokinetic data among critically ill children.

Global epidemiology of pediatric severe sepsis: the sepsis prevalence, outcomes, and therapies study.

RATIONALE: Limited data exist about the international burden of severe sepsis in critically ill children. OBJECTIVES: To characterize the global prevalence, therapies, and outcomes of severe sepsis in pediatric intensive care units to better inform interventional trials. METHODS: A point prevalence study was conducted on 5 days throughout 2013-2014 at 128 sites in 26 countries. Patients younger than 18 years of age with severe sepsis as defined by consensus criteria were included. Outcomes were severe sepsis point prevalence, therapies used, new or progressive multiorgan dysfunction, ventilator- and vasoactive-free days at Day 28, functional status, and mortality. MEASUREMENTS AND MAIN RESULTS: Of 6,925 patients screened, 569 had severe sepsis (prevalence, 8.2%; 95% confidence interval, 7.6-8.9%). The patients' median age was 3.0 (interquartile range [IQR], 0.7-11.0) years. The most frequent sites of infection were respiratory (40%) and bloodstream (19%). Common therapies included mechanical ventilation (74% of patients), vasoactive infusions (55%), and corticosteroids (45%). Hospital mortality was 25% and did not differ by age or between developed and resource-limited countries. Median ventilator-free days were 16 (IQR, 0-25), and vasoactive-free days were 23 (IQR, 12-28). Sixty-seven percent of patients had multiorgan dysfunction at sepsis recognition, with 30% subsequently developing new or progressive multiorgan dysfunction. Among survivors, 17% developed at least moderate disability. Sample sizes needed to detect a 5-10% absolute risk reduction in outcomes within interventional trials are estimated between 165 and 1,471 [corrected] patients per group. CONCLUSIONS: Pediatric severe sepsis remains a burdensome public health problem, with prevalence, morbidity, and mortality rates similar to those reported in critically ill adult populations. International clinical trials targeting children with severe sepsis are warranted.