Renal resistive index by point of care ultrasound to predict sepsis associated acute kidney injury in critically ill children.

BACKGROUND: Sepsis associated acute kidney injury (AKI) is linked with adverse outcomes in the PICU. Doppler-based renal resistive index (RRI) has shown promising results in adults for prediction of AKI. We aimed to explore the performance of RRI in children with sepsis. METHODS: This prospective observational study (March - November 2022) included children aged 1-12 years with sepsis admitted to the PICU. RRI and urine neutrophil gelatinase associated lipocalin (NGAL) were measured within 12 h of admission. Children were followed up for 3 days. AKI (new and persistent) was defined as any child with KDIGO stage 2 or 3 AKI on day 3. RESULTS: We enrolled 90 children but included 79 in final analysis. Two thirds (n = 53, 67%) had septic shock. Median (IQR) age was 6.2 years (4.1-9.2). RRI decreased with increasing age. Twenty-six (33%) children had AKI on day 3. Mean (SD) RRI was higher in the AKI group [0.72 (0.08) vs. 0.65 (0.07), p < 0.001].The area under ROC curve for RRI to detect AKI among the 1-4 year old group was 0.75 (95% CI:0.51, 0.98; p = 0.05) and among the 5-12 year old group was 0.76 (0.62, 0.89; p = 0.001). An RRI 0.71 predicted AKI with 100% sensitivity and 46.2% specificity among the 1-4-year-old group and RRI 0.69 predicted it with 70% sensitivity and 77.5% specificity in the 5-12-year-old group. RRI and eGFR at admission were independent predictors of AKI on multivariable analysis. Urine NGAL 94.8 ng/ml predicted AKI with 76.9% sensitivity and 77.4% specificity and AUROC was 0.74 (0.62, 0.86) among the 1-12-year-old group. CONCLUSIONS: RRI values varied with age. RRI showed good diagnostic accuracy to detect new/persistent AKI on day 3 in children with sepsis; however, it was less precise as an independent predictor.

Severe Pneumonia in PICU Admissions: The Pediatric Acute and Critical Care Medicine Asian Network (PACCMAN) Observational Cohort Study, 2020-2022.

OBJECTIVES: Mortality from pneumonia is three times higher in Asia compared with industrialized countries. We aimed to determine the epidemiology, microbiology, and outcome of severe pneumonia in PICUs across the Pediatric Acute and Critical Care Medicine Asian Network (PACCMAN). DESIGN: Prospective multicenter observational study from June 2020 to September 2022. SETTING: Fifteen PICUs in PACCMAN. PATIENTS: All children younger than 18 years old diagnosed with pneumonia and admitted to the PICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Clinical, microbiologic, and outcome data were recorded. The primary outcome was PICU mortality. Univariate and multivariable logistic regression was performed to investigate associations between PICU mortality and explanatory risk factors on presentation to the PICU. Among patients screened, 846 of 11,778 PICU patients (7.2%) with a median age of 1.2 years (interquartile range, 0.4-3.7 yr) had pneumonia. Respiratory syncytial virus was detected in 111 of 846 cases (13.1%). The most common bacteria were Staphylococcus species (71/846 [8.4%]) followed by Pseudomonas species (60/846 [7.1%]). Second-generation cephalosporins (322/846 [38.1%]) were the most common broad-spectrum antibiotics prescribed, followed by carbapenems (174/846 [20.6%]). Invasive mechanical ventilation and noninvasive respiratory support was provided in 438 of 846 (51.8%) and 500 of 846 (59.1%) patients, respectively. PICU mortality was 65 of 846 (7.7%). In the multivariable logistic regression model, age (adjusted odds ratio [aOR], 1.08; 95% CI, 1.00-1.16), Pediatric Index of Mortality 3 score (aOR, 1.03; 95% CI, 1.02-1.05), and drowsiness (aOR, 2.73; 95% CI, 1.24-6.00) were associated with greater odds of mortality. CONCLUSIONS: In the PACCMAN contributing PICUs, pneumonia is a frequent cause for admission (7%) and is associated with a greater odds of mortality.

Survey of Pediatric Status Epilepticus Treatment Practices and Adherence to Management Guidelines (Pedi-SPECTRUM e-Survey).

Aim: Survey of treatment practices and adherence to pediatric status epilepticus (PSE) management guidelines in India. Methods: This eSurvey was conducted over 35 days (15th October to 20th November 2023) and included questions related to hospital setting; antiseizure medications (ASMs); ancillary treatment; facilities available; etiology; and adherence to PSE management guidelines. Results: A total of 170 respondents participated, majority of them were working in tertiary level hospitals (94.1%) as pediatric intensivists (56.5%) and pediatricians (19.4%), and were in clinical practice for 2-10 years (46.5%). Majority use intravenous (IV) midazolam and levetiracetam as first- and second-line ASMs (67.1 and 51.2%, respectively). In cases with refractory status epilepticus (RSE), the most commonly used ASM is midazolam infusion (92.4%). For super-refractory status epilepticus (SRSE), the commonly used third-line ASMs include midazolam infusion (34.1%), thiopentone infusion (26.5%), high dose phenobarbitone (18.2%), and ketamine infusion (15.3%). Overall, in cases with SRSE, 44.7% respondents use ketamine infusion, 42.5% use add-on oral topiramate, and 34.7% use high-dose phenobarbitone (1-3 mg/kg/hour) infusion. Most respondents targeted both clinical and EEG seizure control (48.8%). Ancillary treatment used for SRSE included IV pyridoxine (57.1%), methylprednisolone (45.3%), IVIG (42.4%), ketogenic diet (40.6%), and second-line immunomodulation (33.5%). Most common causes were febrile SE, viral encephalitis, and febrile illness-related epilepsy syndrome (60.6%, 52.4%, and 37.1%, respectively). Facilities available included pediatric intensive care units (PICU) (97.1%), mechanical ventilation (98.2%), pediatric neurologist (68.8%), MRI brain (86.5%), EEG (69.4%), and viral PCR (58.2%). The compliance with guidelines for timing of initiation of ASM ranged from 63.5 to 88.8%. Conclusion: Intravenous midazolam bolus/es, levetiracetam, and midazolam infusion are commonly used first-, second-, and third-line ASMs, respectively. There were wide variations in use of ASMs for RSE and SRSE, ancillary treatment, and compliance to PSE management guidelines. How to cite this article: Suthar R, Angurana SK, Nallasamy K, Bansal A, Muralidharan J. Survey of Pediatric Status Epilepticus Treatment Practices and Adherence to Management Guidelines (Pedi-SPECTRUM e-Survey). Indian J Crit Care Med 2024;28(5):504-510.

An Observational Study on Pattern of Empirical Acyclovir Therapy in Children With Acute Encephalitis From Northern India.

OBJECTIVES: To identify the prevalence of herpes simplex encephalitis (HSE), factors influencing the duration of empirical acyclovir and frequency of acute kidney injury (AKI) in children with acute encephalitis syndrome (AES). DESIGN: Prospective observational study. SETTING: Pediatric Emergency Department and PICU of a tertiary hospital in Northern India. PATIENTS: All consecutive, eligible children between 1 month and 12 years old presenting with AES, defined as altered consciousness for greater than 24 hours (including lethargy, irritability, or a change in personality) and two or more of the following signs: 1) fever (temperature ≥ 38°C) during the current illness, 2) seizures or focal neurological signs, 3) cerebrospinal fluid (CSF) pleocytosis, 4) electroencephalogram, and/or 5) neuroimaging suggesting encephalitis, who received at least one dose of acyclovir. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 101 children screened, 83 were enrolled. The median (interquartile range [IQR]) age was 3 years (1-6 yr). Thirty-one children (37.3%) were diagnosed with AES, of which four were labeled as probable HSE (three based on MRI brain, one based on serology). Scrub typhus, dengue, Japanese encephalitis, and mumps were the other infective causes. The median (IQR) duration of acyclovir therapy was 72 hours (24-264 hr); 21 children (25.3%) received acyclovir for less than 24 hours and 11 (13.3%) for greater than or equal to 14 days. New-onset AKI was seen in 18 children (21.7%) but was mostly transient. Death ( n = 8, 9.6%) and discontinuation of care due to futility or other reasons ( n = 15, 18%) were noted in 23 children (28%). Factors associated with duration of acyclovir greater than 7 days, on univariable analysis, were lower modified Glasgow Coma Score at admission, requirement of invasive ventilation, invasive intracranial pressure monitoring, and CSF pleocytosis (5-500 cells). On multivariable analysis, only CSF pleocytosis of 5-500 cells was associated with duration of acyclovir greater than 7 days. CONCLUSIONS: Given the low prevalence of HSE, and the risk of AKI, this study sensitizes the need to review our practice on initiation and stopping of empirical acyclovir in children with acute encephalitis.

Clinical Profile, Intensive Care Needs and Outcome of Children with Dilated Cardiomyopathy Associated with Vitamin D Deficiency: A 5-year PICU Experience.

Aim: To describe the clinical profile, treatment details, intensive care needs, and long-term outcome of children with dilated cardiomyopathy (DCM) associated with Vitamin D deficiency (VDD). Materials and methods: Case records of 14 children with DCM associated with VDD [25(OH)D3 levels <20 ng/mL] admitted to the pediatric intensive care unit (PICU) of a tertiary care teaching hospital between January 2017 and December 2021 were retrospectively analyzed for clinical features, echocardiographic findings, treatment details, intensive care needs, and outcomes. Results: The median (IQR) age was 6 (2-9) months and 71% (n=10) were males. The common modes of presentation included respiratory distress or failure (78.6%), congestive cardiac failure (71.4%), cardiogenic shock (37.5%), and seizures and encephalopathy (14.3% each). The median (IQR) serum calcium was 8.7 (7-9.5) mg%, ionized calcium 0.7 (0.7-1.1) mmol/L, alkaline phosphatase 343 (316-415) IU/L, phosphate 3.5 (2.6-4.5) mg%, PTH 115 (66-228) pg/mL, and 25(OH)D3 5 (3-7) ng/mL. The median (IQR) left ventricular ejection fraction (LVEF) at admission was 22 (17-25)%. The treatment included intravenous calcium infusion (35.7%), vitamin D supplementation in all (57.1% parenteral and 42.9% oral), mechanical ventilation (35.7%), and vasoactive drugs (57.1%). There was no mortality. The median (IQR) duration of PICU and hospital stay was 76 (31-98) hours and 6 (4.7-10) days, respectively. Out of 14 children, 10 (71.4%) were followed-up till median (IQR) of 10 (7-58) months. All were asymptomatic and had normal LEVF (except one had residual moderate mitral regurgitation). Conclusion: Vitamin D deficiency is a potentially treatable and reversible cause of DCM in children. How to cite this article: Kumar S, Randhawa MS, Angurana SK, Nallasamy K, Bansal A, Kumar MR, et al. Clinical Profile, Intensive Care Needs and Outcome of Children with Dilated Cardiomyopathy Associated with Vitamin D Deficiency: A 5-year PICU Experience. Indian J Crit Care Med 2023;27(7):510-514.

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.

Severe dengue associated with Staphylococcus aureus sepsis in pediatric patients: a case series.

BACKGROUND: Staphylococcus aureus co-infection is seldom reported in children with severe dengue. METHODOLOGY: In this retrospective study, we reported five children with severe dengue and S. aureus co-infection admitted to pediatric intensive care unit (PICU) during July-December 2021. RESULTS: All children had prolonged fever, persistence of bilateral pleural effusion beyond the critical phase, thrombocytopenia and raised inflammatory markers [C-reactive protein (CRP) and procalcitonin]. S. aureus was isolated from pleural fluid (n = 2, 40%), blood (n = 2, 40%) and endotracheal aspirate (n = 1, 20%). Four children (80%) grew methicillin-sensitive S. aureus, while 1 (20%) had methicillin-resistant S. aureus. Two children (40%) had septic thromboemboli in skin, and 1 (20%) had limb cellulitis. One child required anterior thoracotomy, pericardiectomy and bilateral pleural decortication, while all other children required intercostal chest tube drainage. All children required prolonged targeted antibiotics, invasive mechanical ventilation and had prolong stay in PICU and all of them survived. CONCLUSION: In children with severe dengue, persistence of fever, persistence of pleural effusion beyond critical phase and raised CRP and procalcitonin should raise suspicion of bacterial/S. aureus co-infection.

Clinico-Laboratory Profile, Intensive Care Needs and Short-Term Outcome of Multisystem Inflammatory Syndrome in Children (MIS-C): Experience during First and Second Waves from North India.

OBJECTIVES: To describe the clinico-laboratory profile, intensive care needs and outcome of multisystem inflammatory syndrome in children (MIS-C) during the first and second waves. METHODOLOGY: This retrospective study was conducted in the paediatric emergency and paediatric intensive care unit (PICU) of a tertiary care teaching hospital in North India involving 122 children with MIS-C admitted during the first wave (September 2020-January 2021, n = 40) and second wave (February 2021-September 2021, n = 82) of coronavirus disease 2019 (COVID-19). RESULTS: The median (interquartile range) age was 7 (4-10) years and 67% were boys. Common manifestations included fever (99%), abdominal symptoms (81%), rash (66%) and conjunctival injection (65%). Elevated C-reactive protein (97%), D-dimer (89%), procalcitonin (80%), IL-6 (78%), ferritin (56%), N-terminal pro B-type natriuretic peptide (84%) and positive severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antibody (81%) were common laboratory abnormalities. Cardiovascular manifestations included myocardial dysfunction (55%), shock (48%) and coronary artery changes (10%). The treatment included intensive care support (57%), non-invasive (33%) and invasive (18%) ventilation, vasoactive drugs (47%), intravenous immunoglobulin (IVIG) (83%), steroids (85%) and aspirin (87%). The mortality was 5% (n = 6). During the second wave, a significantly higher proportion had positive SARS-CoV-2 antibody, contact with COVID-19 and oral mucosal changes; lower markers of inflammation; lower proportion had lymphopenia, elevated IL-6 and ferritin; lower rates of shock, myocardial dysfunction and coronary artery changes; lesser need of PICU admission, fluid boluses, vasoactive drugs and IVIG; and shorter hospital stay. CONCLUSION: MIS-C is a febrile multisystemic disease characterized by hyperinflammation, cardiovascular involvement, temporal relationship to SARS-CoV-2 and good outcome with immunomodulation and intensive care. During the second wave, the severity of illness, degree of inflammation, intensive care needs, and requirement of immunomodulation were less as compared to the first wave.

Acute Diarrhea and Severe Dehydration in Children: Does Non-anion-gap Component of Severe Metabolic Acidemia Need More Attention?

Background: Despite significant loss of bicarbonate during acute diarrhea, pediatric data are scarce with acute diarrhea/severe dehydration (ADSD) and severe non-anion-gap metabolic acidemia (sNAGMA). We planned to study their clinical profile, critical care needs, and outcome. Patients: Children (1 month-12 years) with ADSD and sNAGMA (pH <7.2 and/or bicarbonate <15 mEq/L, and normal/mixed anion gap) admitted in Pediatric Emergency Department from January 2016 to December 2018 were enrolled. Children with pure high-anion-gap metabolic acidemia were excluded. Methods: Medical records were reviewed retrospectively. The primary outcome was time taken to resolve acidemia. Secondary outcomes were acute care area free days in 5 days (ACAFD5), and adverse outcome as composite of Pediatric Intensive Care Unit (PICU) admission and/or death. Results: Out of 929 diarrhea patients admitted for intravenous therapy, 121 (13%; median age, 4 months) had ADSD and sNAGMA. Median (IQR) pH was 7.11 (7.01-7.22); 21% patients had pH <7.00. Hyperchloremia (96%) and hypernatremia (45%) were common. About 12% patients each required inotropes and ventilation, while 58% had acute kidney injury (AKI). Median (IQR) time for resolution of acidemia among survivors was 24 (12, 24) hours. Thirty-two patients had adverse outcome. Higher grades of sNAGMA were associated with shock, AKI, coma, hypernatremia, hyperkalemia, adverse outcome, and lesser ACAFD5. Shock, ventilation, renal replacement therapy (RRT), and higher grades of sNAGMA were predictors of adverse outcome, with former two being independent predictors. Conclusion: Severe non-anion-gap metabolic acidemia in children with ADSD is associated with organ dysfunctions, dyselectrolytemias, and lesser ACAFD5. Resolution of acidemia took unacceptably longer time. Higher grades of sNAGMA were a predictor of adverse outcomes. Trials are suggested to assess the role of additional bicarbonate therapy. How to cite this article: Takia L, Baranwal AK, Gupta PK, Angurana SK, Jayashree M. Acute Diarrhea and Severe Dehydration in Children: Does Non-anion-gap Component of Severe Metabolic Acidemia Need More Attention? Indian J Crit Care Med 2022;26(12):1300-1307.

Probiotics and Coronavirus disease 2019: think about the link.

The pandemic of Coronavirus disease 2019 (COVID-19) is rapidly progressing, causing significant morbidity and mortality. Various antiviral drugs, anti-inflammatory drugs and immunomodulators have been tried without substantial clinical benefits. The severe and critical cases of COVID-19 disease are characterised by gut microbiome dysbiosis, immune dysregulation, hyper-inflammation and hypercytokinaemia (cytokine storm). Therefore, the strategies which target these pathophysiological processes may be beneficial. Probiotics are one such strategy that exerts beneficial effects by manipulation of the gut microbiota, suppression of opportunistic pathogens in the gut, decreasing translocation of opportunistic organisms, activation of mucosal immunity and modulation of the innate and adaptive immune response. Probiotics are the potential candidates to be tested in moderate and severe cases of COVID-19 due to several beneficial effects, including easy availability, easy to administer, safe and economical to use.

Effect of early withdrawal of phenobarbitone on the recurrence of neonatal seizures: An open-label randomized controlled trial.

BACKGROUND: The long-term administration of phenobarbitone in neonates may be associated with adverse neurological outcome. The timing of stopping phenobarbitone maintenance after acute seizure control in neonates is a matter of debate. OBJECTIVES: To study the effect of early withdrawal of phenobarbitone on recurrence of neonatal seizures. STUDY DESIGN: Open-label randomized controlled trial. PARTICIPANTS: Outborn neonates (≥34 weeks of gestation to <28 days of postnatal period) with seizures (n = 221) admitted to Neonatal unit in Pediatric emergency of a tertiary care hospital in north India over 1 year. INTERVENTION: After a loading dose of phenobarbitone (20 mg/kg), neonates who remained seizure free for at least 12 h were enrolled after written informed consent from parents, and randomized (computer generated block randomization) to 'phenobarbitone withdrawal group' (n = 112) where phenobarbitone maintenance was stopped and 'phenobarbitone continued group' (n = 109) where phenobarbitone maintenance was continued until discharge and further as per clinician's discretion. OUTCOMES: The primary outcome was seizure recurrence until discharge and secondary outcomes were time to reach full enteral feeds, duration of hospital stay, abnormal neurological status at discharge, and mortality in two groups. RESULTS: The baseline variables were comparable in 2 groups. The incidence of seizure recurrence was similar in the phenobarbitone withdrawal and phenobarbitone continued groups (50% vs. 37.6%, respectively, p = 0.078). Among secondary outcomes, the phenobarbitone withdrawal and continued groups had similar time to reach full enteral feeds (4.02 days vs. 4.2 days, p = 0.75), duration of hospital stay (6.3 days vs. 6.5 days, p = 0.23), abnormal neurological status at discharge (45.6% vs. 38%, p = 0.39), and mortality (11.6% vs. 8.3%, p = 0.50). CONCLUSION: Early withdrawal of phenobarbitone in neonatal seizures does not lead to a significant increase in the rate of seizure recurrence.

Cytokine Levels in Critically Ill Children With Severe Sepsis and Their Relation With the Severity of Illness and Mortality.

OBJECTIVE: To study the baseline cytokine levels and their relation with the severity of illness and mortality in critically ill children with severe sepsis. DESIGN: Subgroup analysis of a randomized, double-blind, placebo-controlled trial. SETTING: Pediatric intensive care unit of a tertiary level teaching hospital in India. PATIENTS: Fifty children with severe sepsis aged 3 months to 12 years. MATERIAL AND METHODS: Blood was collected at admission for estimation of pro-inflammatory (interleukin 6 [IL-6], IL-12p70, IL-17, and tumor necrotic factor α [TNF-α]) and anti-inflammatory (IL-10 and transforming growth factor ß1 [TGF-ß1]) cytokines. PRIMARY OUTCOME: To find out correlation between cytokine levels and severity of illness scores (Pediatric Risk of Mortality [PRISM] III score, Sequential Organ Failure Assessment [SOFA], and Vasoactive-Inotropic Score [VIS]). SECONDARY OUTCOMES: To compare cytokine levels among survivors and nonsurvivors. RESULTS: Baseline pro-inflammatory cytokine levels (median [interquartile range]) were IL-6: 189 (35-285) pg/mL, IL-12p: 48 (28-98) pg/mL, IL-17: 240 (133-345) pg/mL, and TNF-α: 296 (198-430) pg/mL; anti-inflammatory cytokine levels were IL-10: 185 (62-395) pg/mL and TGF-ß1: 204 (92-290) ng/mL. Pro-inflammatory cytokines showed positive correlation with PRISM III score: IL-6 (Spearman correlation coefficient, ρ = 0.273, P = .06), IL-12 (ρ = 0.367, P = .01), IL-17 (ρ = 0.197, P = .17), and TNF-α (ρ = 0.284, P = .05), and anti-inflammatory cytokines showed negative correlation: IL-10 (ρ = -0.257, P = .09) and TGF-ß (ρ = -0.238, P = .11). Both SOFA and VIS also showed weak positive correlation with IL-12 (ρ = 0.32, P = .03 and ρ = 0.31, P = .03, respectively). Among nonsurvivors (n = 5), the levels of all the measured pro-inflammatory cytokines were significantly higher as compared to survivors, IL-6: 359 (251-499) pg/mL versus 157 (97-223) pg/mL, P < .0001, IL-12p70: 167 (133-196) pg/mL versus 66 (30-100) pg/mL, P < .0001, IL-17: 400 (333-563) pg/mL versus 237 (122-318) pg/mL, P = .009, and TNF-α: 409 (355-503) pg/mL versus 330 (198-415) pg/mL, P = .002, respectively. CONCLUSION: In critically ill children with severe sepsis, pro-inflammatory cytokines (especially IL-12p70) showed a weak positive correlation with severity of illness and were significantly higher among nonsurvivors.

Hemophagocytic Lymphohistiocytosis in a PICU of a Developing Economy: Clinical Profile, Intensive Care Needs, Outcome, and Predictors of Mortality.

OBJECTIVES: To describe the clinical profile, intensive care needs, outcome, and predictors of mortality in critically ill children with hemophagocytic lymphohistiocytosis. DESIGN: Retrospective case series. SETTING: PICU of a tertiary care teaching hospital in North India. PATIENTS: Children 2 months to 12 years old with the diagnosis of hemophagocytic lymphohistiocytosis admitted to PICU from January 2012 to April 2019 (7» yr). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Sixty-two children with hemophagocytic lymphohistiocytosis (60 secondary and two primary) were enrolled. The median (interquartile range) age of the study group was 82 months (50.5-124 mo). The median (interquartile range) Pediatric Risk of Mortality III score was 16 (10-23). Majority of hemophagocytic lymphohistiocytosis was infection-associated (n = 51; 82.3%). Among these, scrub typhus accounted for 29% of cases (n = 18), dengue 17.7% (n = 11), bacterial sepsis 14.5% (n = 9), enteric fever 6.5% (n = 4), and other infections 14.5% (n = 9). Systemic-onset juvenile idiopathic arthritis accounted for 9.7% of cases (n = 6) and malignancy for 4.8% patients (n = 3). Majority of cases were treated with steroids (77.4%) and IV immunoglobulin (25.8%). Various complications noted were shock (71%), acute kidney injury (66.1%), acute respiratory distress syndrome (41.9%), disseminated intravascular coagulation (54.8%), CNS dysfunction (54.8%), multiple organ dysfunction syndrome (82.3%), and healthcare-associated infections (14.5%). Intensive care needs for primary illness and/or hemophagocytic lymphohistiocytosis included mechanical ventilation (74.2%); packed RBC (72.3%), fresh frozen plasma (40.3%), and platelet (48.4%) transfusion; vasoactive drugs (71%); and renal replacement therapy (24.2%). The median duration of PICU stay was 5 days (2.5-9.5 d) and mortality was 59.7% (n = 37). On univariate analysis, nonsurvivors had higher Pediatric Risk of Mortality III score; higher proportion of shock, acute kidney injury, acute respiratory distress syndrome, disseminated intravascular coagulation, and multiple organ dysfunction syndrome; the need for blood and blood components, mechanical ventilation, vasoactive drugs, and renal replacement therapy; higher Vasoactive-Inotropic Score; and prolonged duration of mechanical ventilation compared with survivors. CONCLUSIONS: Hemophagocytic lymphohistiocytosis in PICU is commonly secondary to tropical infections and associated with high mortality. Higher severity of illness; shock and multiple organ dysfunction syndrome; need for blood and blood products, mechanical ventilation, vasoactive drugs, and renal replacement therapy; higher Vasoactive-Inotropic Score; and prolonged mechanical ventilation predicted death. Treatment of underlying infection and a less intense immunosuppressive therapy (steroids ± IV immunoglobulin) are suggested options. A high index of suspicion for complicating hemophagocytic lymphohistiocytosis is required in children with prolonged fever, cytopenias, organomegaly, and organ dysfunction not responding to conventional treatment.

Efficacy and Safety of Levetiracetam vs. Phenytoin as Second Line Antiseizure Medication for Pediatric Convulsive Status Epilepticus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: To evaluate the efficacy and safety of levetiracetam (LEV) in comparison to phenytoin (PHT) as second line antiseizure medication (ASM) for Pediatric convulsive status epilepticus (SE). DATA SOURCE: PubMed, Embase, Google scholar/Google, Scopus, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials. STUDY SELECTION: Randomized controlled trials (RCTs) assessing LEV and PHT as second line agent for convulsive SE in children <18 years published between 1 January 2000 and 30 November 2020. DATA EXTRACTION: The data were pooled regarding the proportion of children achieving seizure cessation within 5-60 min of completion of study drug infusion (primary outcome); and seizure cessation within 5 min, time to achieve seizure cessation, seizure recurrence between 1 to 24 h, intubation and cardiovascular instability (secondary outcomes). Data were analyzed using RevMan version 5.4 and quality analysis was done using Cochrane risk-of-bias tool. The study protocol was registered with PROSPERO. DATA SYNTHESIS: Twelve RCTs with 2293 children were included. Seizure cessation within 5-60 min was similar with both the drugs [82% in LEV vs. 77.5% in PHT, risk ratio (RR) = 1.04, 95% confidence interval (95% CI) 0.97-1.11, p = 0.30]. Seizure recurrences within 1-24 h was higher with PHT in comparison to LEV (16.6% vs. 9.7%, RR = 0.63, 95% CI 0.44-0.90, p = 0.01). Higher proportion of children in PHT group required intubation and mechanical ventilation (21.4% vs. 14.2%, RR = 0.54, 95% CI 0.30-0.98, p = 0.04). Seizure cessation within 5 min, time to achieve seizure cessation, and cardiovascular instability were similar with both the drugs. Three RCTs were at low risk of bias and nine were at high risk of bias. CONCLUSION: The efficacy of LEV is similar to PHT as second line ASM for Pediatric convulsive SE. Seizure recurrences between 1 to24 h and requirement of intubation and mechanical ventilation were significantly higher with PHT in comparison to LEV.

Updated Management Protocol for Multisystem Inflammatory Syndrome in Children (MIS-C).

The multisystem inflammatory syndrome in children (MIS-C) is a post-viral immunological or hyper-inflammatory complication of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection commonly seen in older children, who commonly present with fever, multi-systemic involvement including myocardial dysfunction and shock, and hyper-inflammation. The treatment of MIS-C is adapted from the treatment of other immunological or hyper-inflammatory conditions and these treatment protocols are not uniform across the globe, and more so, in India. We propose a uniform management protocol for MIS-C based on our experience of treating MIS-C cases, available evidence till now, and recent guidelines. The aims are to identify children with MIS-C with high sensitivity, recognize other infections or inflammatory processes, stratify treatment based on severity, and manage hyper-inflammatory syndrome.

Intensive Care Needs and Short-Term Outcome of Multisystem Inflammatory Syndrome in Children (MIS-C): Experience from North India.

OBJECTIVES: To describe the intensive care needs and outcome of multisystem inflammatory syndrome in children (MIS-C). METHODOLOGY: This retrospective study was conducted in the pediatric emergency, pediatric intensive care unit (PICUs) and the coronavirus disease 2019 (COVID 19) hospital of a tertiary teaching and referral hospital in North India over a period of 5 months (September 2020 to January 2021). Clinical details, laboratory investigations, intensive care needs, treatment and short-term outcome were recorded. RESULTS: Forty children with median interquartile range age of 7 (5-10) years were enrolled. The common clinical features were fever (97.5%), mucocutaneous involvement (80%), abdominal (72.5%) and respiratory (50%) symptoms. Shock was noted in 80% children. Most cases (85%) required PICU admission where they received nasal prong oxygen (40%), non-invasive (22.5%) and invasive (22.5%) ventilation and vasoactive drug support (72.5%). The confirmation of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) exposure was in the form of positive serology (66.7%), reverse transcriptase polymerase chain reaction (10%), and contact with SARS-CoV-2 positive case (12.5%). The common echocardiographic findings included myocardial dysfunction (ejection fraction <55%; 72.5%), and coronary artery dilatation or aneurysm (22.5%). The immunomodulatory treatment included intravenous immunoglobulin (2 g/kg) (100%) and steroids (methylprednisolone 10-30 mg/kg/day for 3-5 days) (85%). Aspirin was used in 80% and heparin (low molecular weight) in 7.5% cases. Two children died (5%) and median duration of PICU and hospital stay in survivors were 5 (2-8) and 7 (4-9) days, respectively. Children with shock showed higher total leucocyte count and higher rates of myocardial dysfunction. CONCLUSION: Cardiovascular involvement and shock are predominant features in severe disease. Early diagnosis can be challenging given the overlapping features with other diagnoses. A high index of suspicion is warranted in children with constellation of fever, mucocutaneous, gastrointestinal and cardiovascular involvement alongwith evidence of systemic inflammation and recent or concurrent SARS-CoV-2 infection. The short-term outcome is good with appropriate organ support therapies and immunomodulation.

Microorganisms Profile and Antimicrobial Resistance Pattern in Outborn Neonates in Northern India: A Hospital-Based Observational Study.

BACKGROUND: Neonates born somewhere else (outborn) and treated in a referral centre have different microbiological profile. We report the microorganism's profile and antimicrobial resistance (AMR) in blood culture proven sepsis in outborn neonates. METHODS: Culture positive neonatal sepsis from a neonatal unit of a referral institute catering to outborn neonates was studied over an 18 months duration. Data from the hospital information system were used to analyse the culture positivity rates, the spectrum of the microorganisms isolated and AMR pattern. RESULTS: Out of 5258 admitted neonates, 3687 blood samples were sent for suspect sepsis. The blood cultures were positive in 537 (14.6%) samples from 514 neonates. Gram-positive cocci (GPC) were the most common [240 (45%)] followed by gram-negative bacilli (GNB) [233 (43.4%)] and fungi [64 (11.9%)]. Coagulase negative staphylococcus (CONS) contributed to two-thirds of GPC followed by Klebsiella [93 (17.3%)] and Acinetobacter species [52 (9.7%)]. In 403 (75%) neonates, organisms grew in the samples sent at or within 24 h of admission. The case fatality rate was significantly higher in those with culture positive sepsis. The resistance to meropenem and imipenem was documented in 57.1% and 49.7%, respectively and 48% of the GNB was multidrug resistant. CONCLUSIONS: CONS followed by Klebsiella species were the most common organisms isolated. Three-fourths of the neonates had organisms grown at or within 24 h from admission. More than half of the GNB were multidrug resistant. The case fatality rate was significantly higher in those with culture positive sepsis.

Sepsis is the third most common cause of neonatal mortality globally. Outborn neonates differ in their microorganisms' profile and antimicrobial resistance (AMR) pattern in comparison to inborn neonates. In this study, we report the microorganisms profile and their AMR pattern in blood culture proven sepsis in a large cohort of outborn (extramural) neonates admitted to the index institute. We have also presented the state-wise profile and have compared their AMR pattern. Out of the 5258 admitted neonates, 3687 blood samples were sent for culture for suspect sepsis. The blood cultures were positive in 537 (14.6%) samples from 514 neonates. Coagulase-negative staphylococcus (CONS) followed by Klebsiella species were the most common organisms isolated from this large cohort of outborn neonates. More than 75% of the neonates grew the organisms within 24 h from admission indicating that many of them harboured the organisms at admission. Case fatality rate was significantly higher in those neonates with culture positive sepsis in comparison to culture negative sepsis. Close to 50% of the gram-negative bacilli isolates were multidrug resistant and half of them were extensively drug resistant. A significant between-state difference in organism profile and their AMR patterns were observed.

Loop-mediated isothermal amplification (LAMP) in the respiratory specimens for the diagnosis of pediatric pulmonary tuberculosis: A pilot study.

BACKGROUND: Loop-mediated isothermal amplification (LAMP) assay is a novel molecular diagnostic technique that can be used for the diagnosis of tuberculosis (TB). It is most suited for developing countries as it is rapid, inexpensive, highly sensitive, requiring minimal infrastructure, training and manpower. Studies in pediatric TB are lacking. We evaluated LAMP in the diagnosis of pediatric pulmonary TB. METHODOLOGY: This was a cross-sectional analytical study conducted at a tertiary care teaching hospital in North India from July 2014 to June 2015 involving 60 children with suspected pulmonary TB. Respiratory specimens (sputum, gastric lavage, bronchoalveolar lavage and/or endotracheal aspirates) were collected and subjected to BACTEC MGIT 960 culture, IS6110 PCR, and LAMP assay targeting IS6110 gene of Mycobacterium tuberculosis. RESULTS: Thirty seven children had confirmed and probable TB according to the composite reference standard (CRS). Among all the 3 tests used for diagnosis of Pulmonary TB, LAMP had highest sensitivity (37.8%) followed by PCR (27%), and culture (21.6%) when compared against the predefined CRS. Culture had maximum specificity of 100%; and PCR, and LAMP had specificity of 95-96%. The sensitivity, specificity, PPV, and NPV of LAMP against culture as reference standard were 75%, 72.4%, 42.9%, and 91.3% respectively. Similarly sensitivity, specificity, PPV, and NPV of PCR against culture as reference standard were 75%, 86.2%, 60%, and 86.2% respectively. On combining LAMP with culture, sensitivity increased to 45.7% (7.8% increase, p = 0.04). CONCLUSION: We noted that LAMP had highest sensitivity when compared to culture and PCR and comparable specificity.

Better Groundwork Can Avoid Troubled Waters: A Developing Country Perspective on Drowning.

OBJECTIVE: Drowning is a leading cause of unintentional injury-related death in low- and middle-income countries (LMICs). This study was undertaken to know the epidemiology, intensive care needs and predictors of outcome of children with drowning. METHODS: Records of children below 12 years admitted with drowning to the emergency room and/or paediatric intensive care unit (PICU) of a tertiary care hospital in North India were retrospectively analysed. 'Favourable outcome' was defined as normal neurological status at discharge (normal cognition and no motor deficits) and 'unfavourable outcome' as death or abnormal neurological status at discharge. Multivariable analysis was done for predictors of unfavourable outcome. RESULTS: Twenty-seven children were analyzed, 14 (51.8%) were boys. Median (IQR) age was 18 months (12-30). The median (IQR) duration of submersion was 4 min (3-9). Six children (22.2%) presented in pulseless arrest, and 7 (43.7%) had both hypoxaemia (saturation <94% on room air) and encephalopathy (GCS <13) at admission. Ten children (37%) were transferred to PICU; principal indications being hypoxic ischaemic encephalopathy (HIE) (n = 6) and ventilation (n = 4). One child died, four survived with sequalae. Predictors of unfavourable outcome on univariable analysis were hypoxaemia, or pulseless arrest at admission, HIE and need for mechanical ventilation; none of these could predict outcome on multivariable analysis. CONCLUSION: Hypoxaemia or pulseless arrest at admission, HIE and need for ventilation predict unfavourable outcome. Appropriate on-site resuscitation and early stabilization may improve outcome in children with drowning in LMIC.

Pediatric empyema thoracis: What has changed over a decade?

OBJECTIVES: The purposes of this paper are to study clinicobacteriological profile, treatment modalities and outcome of pediatric empyema thoracis and to identify changes over a decade. DESIGN: This is a retrospective study. SETTING: Department of Pediatrics of a tertiary care hospital in North India. PATIENTS: We enrolled 205 patients (1 month-12 years) of empyema thoracis admitted over 5 years (2007-11) and compared the profile with that of a previous study from our institute (1989-98). RESULTS: Pleural fluid cultures were positive in 40% (n = 82) cases from whom 87 isolates were obtained. Staphylococcus aureus was the most common isolate (66.7%). Methicillin-sensitive S. aureus accounted for 56%, Methicillin-resistant S. aureus (MRSA) 10% and gram-negative organisms 18.3% of isolates. Intercostal drainage tube (ICDT) was inserted in 97.5%, intrapleural streptokinase was administered in 33.6%, and decortication performed in 27.8% cases. Duration of hospital stay was 17.2 (±6.3) days, duration of antibiotic (intravenous and oral) administration was 23.8 (±7.2) days and mortality rate was 4%. In the index study (compared with a previous study), higher proportion of cases received parenteral antibiotics (51.7% vs. 23.4%) and ICDT insertion (20.5% vs. 7%) before referral and had disseminated disease (20.5% vs. 14%) and septic shock (11.2% vs. 1.6%), less culture positivity (40% vs. 48%), more MRSA (10.3% vs. 2.5%) and gram-negative organisms (18.4% vs. 11.6%), increased use of intrapleural streptokinase and surgical interventions (27.8% vs. 19.7%), shorter hospital stay (17 vs. 25 days) and higher mortality (3.9% vs. 1.6%). CONCLUSIONS: Over a decade, an increase in the incidence of empyema caused by MRSA has been noticed, with increased use of intrapleural streptokinase and higher number of surgical interventions.