Cidofovir in Severe Hypoxemic Adenoviral Pneumonia.

The authors present a 16-mo-old boy with flu like symptoms, not responding to supportive management and progressed to severe hypoxemic pneumonia. Adenovirus was detected in the nasopharyngeal aspirate. He showed rapid improvement after intravenous cidofovir administration.

Safety and Outcomes of Midline and Peripherally Inserted Central Catheters in a Pediatric Intensive Care Unit.

OBJECTIVES: We describe our experience with use of midline catheters in PICU and compare the performance of midline catheters to peripherally inserted central catheters (PICC). METHODS: A review of hospital records was done to including all pediatric patients admitted in the pediatric intensive care unit of a tertiary care centre who underwent placement of midline catheters or PICC, over a period of 18 months (July, 2019 to January, 2021). Patient details, indication, type of catheter and number of attempts at insertion, type and number of infusions administered, dwell time and complications were retrieved from the records. Comparison was made between the midline and PICC groups. RESULTS: The median (IQR) age of children was 7 (3-12) years (75.5% males). 161 midline catheters and 104 PICC were inserted with first attempt success rates of 87.6% and 78.8%, respectively. Median cubital vein was used for majority of the insertions (52.8%). Common complications with midline catheters were pain (n=9, 5.6%), blockage (n=8, 5%) and thrombophlebitis (n=6, 3.7%). Median (interquartile range) dwell time in midline group was 7 (5-10) days. The duration of backflow and dwell time were higher in the PICC group compared to midline group (5.5 vs 3 days; P<0.001 and 9 vs 7 days; P<0.001, respectively). CONCLUSION: Retrospective data showed that midline catheters had good utility in PICU, especially in moderately sick children (PRISM score up to 12), and provide a secure intravenous access, which can last for a week.

In-hospital mortality risk stratification in children aged under 5 years with pneumonia with or without pulse oximetry: A secondary analysis of the Pneumonia REsearch Partnership to Assess WHO REcommendations (PREPARE) dataset.

OBJECTIVES: We determined the pulse oximetry benefit in pediatric pneumonia mortality risk stratification and chest-indrawing pneumonia in-hospital mortality risk factors. METHODS: We report the characteristics and in-hospital pneumonia-related mortality of children aged 2-59 months who were included in the Pneumonia Research Partnership to Assess WHO Recommendations dataset. We developed multivariable logistic regression models of chest-indrawing pneumonia to identify mortality risk factors. RESULTS: Among 285,839 children, 164,244 (57.5%) from hospital-based studies were included. Pneumonia case fatality risk (CFR) without pulse oximetry measurement was higher than with measurement (5.8%, 95% confidence interval [CI] 5.6-5.9% vs 2.1%, 95% CI 1.9-2.4%). One in five children with chest-indrawing pneumonia was hypoxemic (19.7%, 95% CI 19.0-20.4%), and the hypoxemic CFR was 10.3% (95% CI 9.1-11.5%). Other mortality risk factors were younger age (either 2-5 months [adjusted odds ratio (aOR) 9.94, 95% CI 6.67-14.84] or 6-11 months [aOR 2.67, 95% CI 1.71-4.16]), moderate malnutrition (aOR 2.41, 95% CI 1.87-3.09), and female sex (aOR 1.82, 95% CI 1.43-2.32). CONCLUSION: Children with a pulse oximetry measurement had a lower CFR. Many children hospitalized with chest-indrawing pneumonia were hypoxemic and one in 10 died. Young age and moderate malnutrition were risk factors for in-hospital chest-indrawing pneumonia-related mortality. Pulse oximetry should be integrated in pneumonia hospital care for children under 5 years.

Clinical Profile and Predictors of Outcome in Children with Acute Fulminant Myocarditis Receiving Intensive Care: A Single Center Experience.

Acute myocarditis in children is associated with high morbidity and mortality, with limited data on intravenous immunoglobulin (IVIG) treatment and outcome. Our goal was to describe clinical, treatment profile, and predictors of outcome in children with acute fulminant myocarditis (AFM) receiving intensive care. Case records of 120 children with clinical diagnosis of acute myocarditis from January 2008 to December 2018 were analyzed retrospectively. AFM was seen in 89 (74.2%) children of which nearly two-thirds (54 [60.7%]) were hypotensive at admission. The median (interquartile range [IQR]) ejection fraction on echocardiography was 25 (18.5-36%). Eighty-two children (68.3%) received IVIG. Intensive care needs were mechanical ventilation ( n = 71; 59.2%) and inotrope support ( n = 89; 74.2%); median inotrope score being 30 (IQR: 20-55). Twenty-one children died (17.5%). Fever ( p = 0.004), arrhythmia ( p = 0.03), shock ( p = 0.015), higher inotrope score ( p = 0.0001), need for ventilation ( p = 0.025), acidosis ( p = 0.013), AKI ( p = 0.0001), transaminitis ( p = 0.0001), and multiorgan dysfunction ( p = 0.0001) were associated with mortality. The mortality was significantly less in IVIG treated group (12.1 vs. 28.9%; p = 0.02). On multiple logistic regression, MODS ( p = 0.002) was independent predictor of mortality while IVIG treatment ( p = 0.004) was favorably associated with survival. AFM complicated by multiorgan dysfunction carried a poor prognosis. IVIG was associated with survival benefit.

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)).

Scrub Typhus Associated with Guillain-Barré Syndrome (GBS).

Scrub typhus is a vector-borne disease caused by Orientia tsutsugamushi. Clinical manifestations generally occur due to vasculitis and inflammation and can have variable degrees of systemic involvement. Meningoencephalitis and cerebellitis are well-known neurological manifestations of scrub typhus, but the occurrence of Guillain-Barré syndrome is extremely rare. The authors report a 7-y-old boy who developed fever followed by rapidly progressive ascending quadriparesis with areflexia and whose etiological workup revealed positive IgM scrub typhus antibody, as well as, a high OXK titer (1:80). Nerve-conduction studies in all four limbs were suggestive of demyelinating neuropathy. He showed complete recovery after treatment with intravenous immunoglobulin (2 g/kg) and azithromycin.

Detection of IEMs by Mass Spectrometry Techniques in High-Risk Children: A Pilot Study.

OBJECTIVES: To determine the incidence and types of inborn errors of metabolism (IEMs) in high-risk children using mass spectrometry techniques. METHODS: Children considered high-risk for IEM were screened for metabolic diseases during a 3-y period. Dried blood spots and urine samples were analyzed by tandem mass spectrometry (LC-MS/MS) and gas chromatograph-mass spectrometry (GCMS). Samples with abnormal amino acids were confirmed by high-performance liquid chromatography (HPLC). RESULTS: Eight hundred and twenty-two suspected cases were evaluated; of which, 87 possible cases of IEMs were identified. Homocystinuria (n = 51) was the most common IEM detected followed by biotinidase deficiency (n = 7), glutaric aciduria type 1 (n = 7), and carnitine uptake defect (n = 6). Overall, there were 45 (51.7%) cases of organic acidemia, 31 cases (35.6%) of amino acid defect, 9 (10.3%) cases of fatty-acid oxidation disorders, and 2 (2.3%) cases of probable mitochondrial disorder. CONCLUSION: IEMs are common in India, with a hospital-based incidence of 1 in approximately 6642 among high-risk children. Screening of high-risk children by mass spectrometry techniques is a valuable strategy for early diagnosis of IEMs where universal newborn screening is not yet available.

Derivation and validation of a novel risk assessment tool to identify children aged 2-59 months at risk of hospitalised pneumonia-related mortality in 20 countries.

INTRODUCTION: Existing risk assessment tools to identify children at risk of hospitalised pneumonia-related mortality have shown suboptimal discriminatory value during external validation. Our objective was to derive and validate a novel risk assessment tool to identify children aged 2-59 months at risk of hospitalised pneumonia-related mortality across various settings. METHODS: We used primary, baseline, patient-level data from 11 studies, including children evaluated for pneumonia in 20 low-income and middle-income countries. Patients with complete data were included in a logistic regression model to assess the association of candidate variables with the outcome hospitalised pneumonia-related mortality. Adjusted log coefficients were calculated for each candidate variable and assigned weighted points to derive the Pneumonia Research Partnership to Assess WHO Recommendations (PREPARE) risk assessment tool. We used bootstrapped selection with 200 repetitions to internally validate the PREPARE risk assessment tool. RESULTS: A total of 27 388 children were included in the analysis (mean age 14.0 months, pneumonia-related case fatality ratio 3.1%). The PREPARE risk assessment tool included patient age, sex, weight-for-age z-score, body temperature, respiratory rate, unconsciousness or decreased level of consciousness, convulsions, cyanosis and hypoxaemia at baseline. The PREPARE risk assessment tool had good discriminatory value when internally validated (area under the curve 0.83, 95% CI 0.81 to 0.84). CONCLUSIONS: The PREPARE risk assessment tool had good discriminatory ability for identifying children at risk of hospitalised pneumonia-related mortality in a large, geographically diverse dataset. After external validation, this tool may be implemented in various settings to identify children at risk of hospitalised pneumonia-related mortality.

Deciphering the TLR transcriptome and downstream signaling pathway in cerebrospinal fluid in pediatric meningitis.

OBJECTIVE/DESIGN: Pediatric meningitis is characterized by a colossal inflammatory response to the pathogen in the central nervous system (CNS). This unabated inflammatory response persists even after the removal of the pathogen by antibiotics/steroids causing collateral damage to CNS tissue. Toll-like receptors (TLRs) are the key players in the recognition and elicitation of innate-immune response against bacterial/viral components in cerebrospinal fluid (CSF). Till date, the precise understanding of TLR-triggered inflammatory response in pediatric meningitis is lacking. The present study was designed to delineate the role of TLR transcriptome and downstream signaling pathways in CSF of pediatric meningitis. METHODS: Children in the age group of > 3 months to 12 years with pediatric meningitis were included. A total of 249 cases of pediatric meningitis (bacterial = 89, viral = 160) were included. In addition, 71 children who tested negative to the pathogen in CSF tap and did not have signs of infection clinically constituted the controls. RNA was extracted from the CSF samples of both cases and controls. The relative gene expression profile of 42 TLR signaling pathway genes was performed. For the analysis of secretory cytokines and chemokines in CSF, Luminex assay was performed. RESULTS: We report global upregulation of TLR genes in patients with acute bacterial meningitis (ABM). The downstream signaling molecules were upregulated as well. The CSF of pediatric ABM patients revealed a predominant pro-inflammatory milieu marked by increased levels of pro-inflammatory cytokines. A significant correlation between poor clinical outcomes of patients and an increased expression of TLR/pro-inflammatory cytokine genes was observed. CONCLUSION: Our findings provide support for future studies exploring TLR-based adjunct therapy to limit the neurological sequelae, owing to persistent inflammation in pediatric ABM patients.

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.

External validation of the RISC, RISC-Malawi, and PERCH clinical prediction rules to identify risk of death in children hospitalized with pneumonia.

BACKGROUND: Existing scores to identify children at risk of hospitalized pneumonia-related mortality lack broad external validation. Our objective was to externally validate three such risk scores. METHODS: We applied the Respiratory Index of Severity in Children (RISC) for HIV-negative children, the RISC-Malawi, and the Pneumonia Etiology Research for Child Health (PERCH) scores to hospitalized children in the Pneumonia REsearch Partnerships to Assess WHO REcommendations (PREPARE) data set. The PREPARE data set includes pooled data from 41 studies on pediatric pneumonia from across the world. We calculated test characteristics and the area under the curve (AUC) for each of these clinical prediction rules. RESULTS: The RISC score for HIV-negative children was applied to 3574 children 0-24 months and demonstrated poor discriminatory ability (AUC = 0.66, 95% confidence interval (CI) = 0.58-0.73) in the identification of children at risk of hospitalized pneumonia-related mortality. The RISC-Malawi score had fair discriminatory value (AUC = 0.75, 95% CI = 0.74-0.77) among 17 864 children 2-59 months. The PERCH score was applied to 732 children 1-59 months and also demonstrated poor discriminatory value (AUC = 0.55, 95% CI = 0.37-0.73). CONCLUSIONS: In a large external application of the RISC, RISC-Malawi, and PERCH scores, a substantial number of children were misclassified for their risk of hospitalized pneumonia-related mortality. Although pneumonia risk scores have performed well among the cohorts in which they were derived, their performance diminished when externally applied. A generalizable risk assessment tool with higher sensitivity and specificity to identify children at risk of hospitalized pneumonia-related mortality may be needed. Such a generalizable risk assessment tool would need context-specific validation prior to implementation in that setting.

Comparison of Five Different Electrophysiological Criteria for Childhood Guillain Barre Syndrome.

BACKGROUND: Internationally approved electrodiagnostic criteria for Guillain Barre syndrome lack in children. We intended to compare the diagnostic accuracy of the currently available five electrophysiological criteria for childhood Guillain Barre Syndrome (GBS) at the time of sentinel assessment. METHODOLOGY: In this single-center study, data of children diagnosed with GBS between January 2013 to December 2017 were retrieved. Patient charts were reviewed for clinical features, electrophysiological recordings. The electrodiagnostic results (4 motor nerves and two sensory nerves in upper limbs and lower limbs) were reanalyzed and were classified based on Dutch group; Ho; Hadden; Hughes and Rajabally criteria for GBS. RESULTS: During this study period, of the 205 children with clinical features of GBS, 15 children had incomplete electrophysiological data, and four children were excluded due to missing data. The mean age of onset of the 186 children enrolled was 77 months; the median duration from symptom onset to electrodiagnostic evaluation was seven days; pure motor and motor-sensory form of GBS was seen in 71 and 115 children. Based on the Hadden criteria, a demyelinating pattern was noted in 57 children; axonal in 37; Inexcitable in 84 and Equivocal in 8 children. The sensitivity of the various criteria ranged from 71% to 100% for demyelination, 97% to 100% for axonal. The degree of agreement using Hadden and Rajabally criteria for Equivocal subtypes was 0.93. CONCLUSIONS: The Rajabally criteria showed the best sensitivity, specificity and diagnostic accuracy for electrodiagnosis of GBS in children when compared against Hadden criteria.

Validation of the pediatric refractory septic shock definition: post hoc analysis of a controlled trial.

BACKGROUND: The European Society of Pediatric and Neonatal Intensive Care (ESPNIC) developed and validated a definition of pediatric refractory septic shock (RSS), based on two septic shock scores (SSS). Both bedside SSS (bSSS) and computed SSS (cSSS) were found to be strongly associated with mortality. We aimed at assessing the accuracy of the RSS definition on a prospective cohort from India. METHODS: Post hoc analysis of a cohort issued from a double-blind randomized trial that compared first-line vasoactive drugs in children with septic shock. Sequential bSSS and cSSS from 60 children (single-center study, 53% mortality) were analyzed. The prognostic value of the ESPNIC RSS definition was tested for 28-day all-cause mortality. RESULTS: In this septic shock cohort, RSS was diagnosed in 35 patients (58.3%) during the first 24 h. Death occurred in 30 RSS patients (85.7% mortality) and in 2 non-RSS patients (8% mortality), OR = 60.9 [95% CI: 10.5-676.2], p < 0.001 with a median delay from sepsis onset of 3 days [1.0-6.7]. Among patients diagnosed with RSS, the mortality was not significantly different according to vasopressors randomization. Diagnosis of RSS with bSSS and cSSS had a high discrimination for death with an area under the receiver operating curve of 0.916 [95% CI: 0.843-0.990] and 0.925 [95% CI: 0.845-1.000], respectively. High prognostic accuracy of the bSSS was found in the first hours following intensive care admission. The best interval of prognostication occurs after the 12th hour following treatment initiation (AUC 0.973 [95% CI: 0.925-1.000]). CONCLUSIONS: The ESPNIC refractory septic shock definition accurately identifies, within the first 6 h of septic shock management, children with lethal outcome.

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.

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.

Intensive care needs and long-term outcome of pediatric toxic epidermal necrolysis - A 10-year experience.

BACKGROUND: Toxic epidermal necrolysis (TEN) is a life-threatening severe cutaneous adverse reaction. Data on pediatric TEN is limited. METHODS: Case records of 44 children, 1 month-12 years with a diagnosis of TEN (>30% body surface area [%BSA] detachment) admitted to a tertiary pediatric intensive care unit (PICU) between 2009 and 2018 were analyzed retrospectively. The primary outcome was mortality, and secondary outcomes were organ dysfunction, length of stay (LOS), and long-term sequelae. RESULTS: Median (IQR) age was 6.5 (3.6, 8.0) years, and 25 (57%) were boys. Median (IQR) %BSA involved, SCORTEN score, and PRISM-III were 65% (45, 80); 2 (2, 3) and 13 (10, 16), respectively. Antiepileptics (n = 24, 54.6%) and antimicrobials (n = 8, 18.2%) were the most common offending agents. Twenty-four (54.5%) children had culture positive sepsis. Immunomodulatory therapy was provided in 35 (79.5%) and conservative management in nine (20.5%) children. Intravenous immunoglobulin (IVIG) was given in 22 (50%), steroids in three (6.8%), and both IVIG and steroids in 10 (22.7%) children. Respiratory failure (n = 14, 31.8%) was the commonest organ failure. Mortality was 15.9% (n = 7), and median (IQR) PICU-LOS in survivors was 8 (4, 11.75) days. There was no association between IVIG, steroids, or conservative management with mortality or LOS. Ocular sequelae (n = 20, 54.1%) were the most common long-term complication followed by skin (18, 40.1%). CONCLUSION: Immunomodulation with IVIG or steroids was not associated with any mortality benefit as compared to conservative management alone. Further research is required to determine the most effective treatment in pediatric TEN.

Randomized Clinical Trial of 20% Mannitol Versus 3% Hypertonic Saline in Children With Raised Intracranial Pressure Due to Acute CNS Infections.

OBJECTIVES: Mannitol is a commonly used osmotherapy agent in raised intracranial pressure. However, the side effects of mannitol are significant. In traumatic brain injury (adult and pediatric), hypertonic saline (3%) shows varied results in comparison with 20% mannitol. We compared the effect of 3% hypertonic saline versus 20% mannitol (using common dosing strategies) on raised intracranial pressure in pediatric acute CNS infections. DESIGN: Open-label randomized controlled trial. SETTING: PICU of a quaternary care academic institute. PATIENTS: Children 1-12 years old, with raised intracranial pressure and modified-Glasgow Coma Scale scores less than or equal to 8, were enrolled. INTERVENTIONS: Patients were randomly assigned to 20%-mannitol (n = 28), 0.5 gram/kg/dose versus 3%-hypertonic saline (n = 29), 10 mL/kg loading followed by 0.5-1 mL/kg/hr infusion. An intraparenchymal catheter was used to monitor the intracranial pressure. The primary outcome was the proportion of patients achieved target average intracranial pressure less than 20 mm Hg during 72 hours. Secondary outcomes were interventions, morbidity, and mortality. MEASUREMENTS AND MAIN RESULTS: The proportion of patients with target average intracranial pressure (< 20 mm Hg) was higher in hypertonic saline-group as compared to mannitol-group (79.3% vs 53.6%; adjusted hazard ratio 2.63; 95% CI: 1.23-5.61). Mean (± SE) reduction of intracranial pressure (-14.3 ± 1.7 vs -5.4 ± 1.7 mm Hg; p ≤ 0.001) and elevation of cerebral perfusion pressure (15.4 ± 2.4 vs 6 ± 2.4 mm Hg; p = 0.007) from baseline were significant in hypertonic saline-group. Mean (± SE) intracranial pressure over 72 hours was lower (14 ± 2 vs 22 ± 2 mm Hg; p = 0.009), and cerebral perfusion pressure was higher (65 ± 2.2 vs 58 ± 2.2; p = 0.032) in hypertonic saline-group. Hypertonic saline-group had higher modified-Glasgow Coma Scale score at 72 hours (median, interquartile range 10; 7-11 vs 7; 3-9; p = 0.003), lower mortality (20.7% vs 35.7%; p = 0.21), shorter duration of mechanical ventilation (5 vs 15 d; p = 0.002), and PICU stay (11 vs 19 d; p = 0.016) and less severe neurodisability at discharge (31% vs 61%; p = 0.049). CONCLUSIONS: In pediatric acute CNS infections, 3%-hypertonic saline was associated with a greater reduction of intracranial pressure as compared to 20% mannitol.