High-flow nasal oxygen in infants and children for early respiratory management of pneumonia-induced acute hypoxemic respiratory failure: the CENTURI randomized clinical trial.

Objective: To compare the effectiveness of early high-flow nasal cannula (HFNC) and low-flow oxygen support (LFOS) in children under 5 years with acute hypoxemic respiratory failure (AHRF) due to severe community-acquired pneumonia in low-middle-income countries. Methods: An open-label randomized clinical trial enrolled children aged 2-59 months with AHRF due to severe community-acquired pneumonia and randomized into HFNC and LFOS. In the LFOS group, the patient received cold wall oxygen humidified by bubbling through sterile water administered through simple nasal prongs at a fixed flow rate of 2 L/min. In the HFNC group, the patient received humidified, heated (37 °C), high-flow oxygen at a flow rate assigned based on weight range, with a titratable oxygen fraction. The primary outcome was treatment failure in 72 h (escalating the respiratory support method using any modality other than primary intervention). Results: Data was analyzed intention-to-treat (HFNC = 124; LFOS = 120). Median (IQR) age was 12 (6-20) and 11 (6-27) months, respectively. Treatment failure occurred in a significantly lower proportion in the HFNC group (7.3%, n = 9/124) as compared to the LFOS group (20%, n = 24/120) (relative risk = 0.36, 95% CI 0.18 to 0.75; p = 0.004; adjusted hazard ratio 0.34, 95% CI 0.16 to 0.73; p = 0.006). The intubation rate was significantly lower in the HFNC group (7.3%, n = 9/124 vs. 16.7%, n = 20/120; relative risk = 0.44, 95% CI 0.21 to 0.92, p = 0.023). There were no significant differences noted in other secondary outcomes. No mortality occurred. Conclusion: High-flow nasal cannula oxygen therapy used as early respiratory support in children under 5 years with acute hypoxemic respiratory failure due to severe community-acquired pneumonia was associated with significantly lower treatment failure compared with standard low-flow oxygen support. Trial registration: CTRI/2016/04/006788. Registered 01 April 2016, https://ctri.nic.in/Clinicaltrials/advsearch.php. Supplementary Information: The online version contains supplementary material available at 10.1007/s44253-024-00031-8.

High-Flow Nasal Cannula Versus Nasal Prong Bubble Continuous Positive Airway Pressure in Children With Moderate to Severe Acute Bronchiolitis: A Randomized Controlled Trial.

OBJECTIVES: To compare high-flow nasal cannula (HFNC) versus nasal prong bubble continuous positive airway pressure (b-CPAP) in children with moderate to severe acute bronchiolitis. DESIGN: A randomized controlled trial was carried out from August 2019 to February 2022. (Clinical Trials Registry of India number CTRI/2019/07/020402). SETTING: Pediatric emergency ward and ICU within a tertiary care center in India. PATIENTS: Children 1-23 months old with moderate to severe acute bronchiolitis. INTERVENTION: Comparison of HFNC with b-CPAP, using a primary outcome of treatment failure within 24 hours of randomization, as defined by any of: 1) a 1-point increase in modified Wood's clinical asthma score (m-WCAS) above baseline, 2) a rise in respiratory rate (RR) greater than 10 per minute from baseline, and 3) escalation in respiratory support. The secondary outcomes were success rate after crossover, if any, need for mechanical ventilation (invasive/noninvasive), local skin lesions, length of hospital stay, and complications. RESULTS: In 118 children analyzed by intention-to-treat, HFNC (n = 59) versus b-CPAP (n = 59) was associated with a lower failure rate (23.7% vs. 42.4%; relative risk [95% CI], RR 0.56 [95% CI, 0.32-0.97], p = 0.031). The Cox proportion model confirmed a lower hazard of treatment failure in the HFNC group (adjusted hazard ratio 0.48 [95% CI, 0.25-0.94], p = 0.032). No crossover was noted. A lower proportion escalated to noninvasive ventilation in the HFNC group (15.3%) versus the b-CPAP group (15.3% vs. 39% [RR 0.39 (95% CI, 0.20-0.77)], p = 0.004). The HFNC group had a longer median (interquartile range) duration of oxygen therapy (4 [3-6] vs. 3 [3-5] d; p = 0.012) and hospital stay (6 [5-8.5] vs. 5 [4-7] d, p = 0.021). No significant difference was noted in other secondary outcomes. CONCLUSION: In children aged one to 23 months with moderate to severe acute bronchiolitis, the use of HFNC therapy as opposed to b-CPAP for early respiratory support is associated with a lower failure rate and, secondarily, a lower risk of escalation to mechanical ventilation.

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

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

Threshold of Inotropic Score and Vasoactive-Inotropic Score for Predicting Mortality in Pediatric Septic Shock.

OBJECTIVE: To determine the threshold of the inotropic score (IS) and vasoactive-inotropic score (VIS) for predicting mortality in pediatric septic shock. METHOD: This retrospective cohort study included children aged 1 mo to 13 y with septic shock, requiring vasoactive medication. The area under curve receiver operating characteristic (AUROC) was calculated using mean IS and mean VIS to predict PICU mortality, and Youden index cut points were generated. Sensitivity, specificity, and binary regression analysis were performed. RESULTS: A total of 176 patients were enrolled (survivor, n = 72, 41% and nonsurvivor, n = 104, 59%). For predicting the PICU mortality, AUROC (95% CI) of IS was 0.80 (0.74-0.86) [sensitivity of 88.5 (80.7-94) and specificity of 58.3 (46.1-69.8)] and AUROC of VIS was 0.88 (0.82-0.92) [sensitivity of 83.7 (75.1-90.2) and specificity of 80.6 (69.5-89)]. The respective cutoff scores of IS and VIS were 28 and 42.5. On regression analysis (adjusted odds ratio, 95% CI), illness severity (PRISM-III) (1.12, 1.05-1.12), worst lactate value (1.31, 1.08-1.58), IS (> 28) (3.98, 1.24-12.80), and VIS (> 42.5) (4.66, 1.57-13.87) independently predicted the PICU mortality (r2 = 0.625). CONCLUSION: Threshold of inotropic score (> 28) and vasoactive-inotropic score (> 42.5) were independently associated with PICU mortality. In addition to IS and VIS, severity and worst lactate value independently predicted septic shock mortality in PICU.

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

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

Modified Schwartz formula and 99mTc-DTPA plasma clearance methods to calculate glomerular filtration rate in critically ill children.

BACKGROUND: Studies comparing the modified Schwartz formula with measured GFR (m-GFR) are lacking in critically ill children. METHODS: This prospective cohort study enrolled children aged 1 month to 12 years, within 24 h of admission. m-GFR measured by technetium-99m-labeled diethylenetriaminepentaacetic acid (99mTc-DTPA) and calculated by Russell's two-sample slope-intercept method. Serum creatinine was estimated by modified Jaffe method and estimated GFR (e-GFR) calculated by modified Schwartz formula. The primary outcome was to find agreement between the two methods. Bias, precision, and accuracy were calculated. Secondary outcomes were the incidence of AKI (by p-RIFLE criteria) and the difference between the two methods to diagnose AKI. RESULTS: A total of 208 pairs were analyzed. e-GFR showed good agreement with m-GFR with a mean bias of -4.37 ml/min/1.73 m2 and precision (SD of bias) of 33.07, 95% limit of agreement -69.18 to 60.45, and intraclass correlation of 74% (95%CI 66-80%, P < 0.001). e-GFR underestimated m-GFR by 19.8% (95% CI 7.9-31.7%). Accuracy of e-GFR values within 10%, 20%, and 30% of m-GFR were 68.3%, 72.6%, and 78.8%, respectively. Incidence of AKI within 24 h was 60.1% by e-GFR and 54.3% by m-GFR (kappa 0.569, P < 0.001; sensitivity of 85.8%, 95%CI (78-91.7%). CONCLUSIONS: The modified Schwartz formula shows good agreement with 99mTc-labeled DTPA double plasma sample clearance method for calculating GFR in critically ill children aged 1 month to 12 years. The underestimation of GFR should be kept in mind while applying the formula at the bedside in PICU. TRIAL REGISTRATION: Protocol accessible at Clinical Trial Registry of India (CTRI) www.ctri.nic.in . (Trial Registered Prospectively and Registration No. CTRI/2017/10/010014) ([Registered on: 06/10/2017] Trial Registered Prospectively.) (Title "Measured glomerular filtration rate using Diethylenetriaminepentaacetic acid (DTPA) renal scan versus estimated glomerular filtration rate using modified Schwartz formula in critically ill children: A prospective observational, analytical study."). A higher resolution version of the Graphical abstract is available as Supplementary information.

Prospective Cohort Study on Cumulative Fluid Balance and Outcome in Critically Ill Children Using a Restrictive Fluid Protocol.

OBJECTIVE: To study the association of cumulative fluid balance and clinical outcomes in a pediatric intensive care unit (PICU) practicing restrictive fluid protocol. METHODS: In this prospective cohort study, children aged less than 13 y admitted for more than 48 h were screened. Children with unstable hemodynamics throughout the stay were excluded. Fluid balance was calculated by percentage fluid overload (%FO) for the first 7 d. Patients were divided into positive fluid and negative fluid balance groups. The primary outcome was all-cause 28-d mortality. RESULTS: A total of 888 patients (positive fluid balance group = 531, negative fluid balance group = 357) were analyzed. Mean (SD) cumulative %FO was 1.52 (0.67) vs. -1.18 (0.71), p = < 0.001, and minimum and maximum cumulative %FO were -3.0% and 3.1%, respectively. There was no significant difference in all-cause 28-d mortality between the two groups (n = 104/531, 19.6% vs. n = 60/357, 16.8%, RR = 1.17, 95% CI 0.87 to 1.55; p = 0.29). There was no difference in organ dysfunction [mean (SD) sequential organ failure assessment (SOFA) score 3.3 (0.7) vs. 3.3 (0.6)], acute kidney injury (65% vs. 63.6%), need for renal replacement therapy (14% vs. 13%), and duration of ventilation (median, IQR 4, 2-6 vs. 4, 2-6 d). Longer stay in PICU (5, 3-9 vs. 4, 3-7 d; p = 0.014) and in hospital (8, 5-11 vs. 7, 4-10 d; p = 0.007) were noted in the positive fluid balance group. CONCLUSION: Cumulative fluid balance within 3% using restrictive fluid protocol was not associated with a significant difference in PICU mortality and morbidity.

Effect of Sepsis on Iron Parameters in a Population with High Prevalence of Malnutrition and Iron Deficiency: A Cross-Sectional Case-Control Pilot Study.

There is lack of data on iron metabolism in critically ill sepsis children from population with high prevalence of iron deficiency (ID). The study was designed to study impact of sepsis on iron parameters in children with ID. Sepsis patients (age 6-59 months) and their apparently healthy sibling/cousin as controls were enrolled in this case-control pilot study. Serum iron, TIBC, transferrin saturation, ferritin and sTfR were measured in the two groups. sTfR-Ferritin index was calculated. Patients (n = 134) were significantly underweight compared to controls (n = 54) (WAZ score < - 2; 58% vs. 28%; p < 0.001). Serum iron and sTfR (mg/L) were lower [71.5 (51.0, 115.0) vs. 87.0 (64.5, 130.5), p = 0.068; 3.1 (2.1, 4.5) vs. 3.5 (2.8, 4.8), p = 0.026 respectively] while serum ferritin was higher [229 (94, 484.5) vs. 22 (9.2, 51); p < 0.001] in patients compared to controls. sTfR-Ferritin index was lower in patients [1.3 (0.8, 2.3) vs. 2.5 (1.8, 4.5); p < 0.001]. ROC AUC (patients vs. controls) were 0.89 (95% CI 0.83-0.95) and 0.76 (95% CI 0.68-0.85) for ferritin and sTfR-ferritin index respectively. Survivors and non-survivors were similar in terms of iron parameters. Sepsis-induced alterations in iron parameters among ID children are complex. Qualitatively it is similar (with quantitative differences) to non-ID adult population. Lack of correlation of iron parameters with mortality may be due to ID-associated immune dysfunction.

Early Goal-Directed Therapy With and Without Intermittent Superior Vena Cava Oxygen Saturation Monitoring in Pediatric Septic Shock: A Randomized Controlled Trial.

OBJECTIVE: To compare early goal-directed therapy (EGDT) 'with' and 'without' intermittent superior vena cava oxygen saturation (ScvO2) monitoring in pediatric septic shock. DESIGN: Open label randomized controlled trial. SETTING: Pediatric intensive care unit in a tertiary care center. PARTICIPANTS: Children aged 1 month to 12 year with septic shock. INTERVENTION: Patients not responding to fluid resuscitation (up to 40 mL/kg) were randomized to EGDT 'with' (n=59) and 'without' (n=61) ScvO2 groups. Resuscitation was guided by ScvO2 monitoring at 1-hour, 3-hour, and later on six-hourly in the 'with' ScvO2 group, and by clinical variables in the 'without' ScvO2 group. OUTCOME: Primary outcome was all-cause 28-day mortality. Secondary outcomes were time to and proportion of patients achieving therapeutic endpoints (at 6 hours and PICU stay), need for organ supports, new organ dysfunction (at 24 hours and PICU stay), and length of PICU and hospital stay. RESULTS: The study was stopped after interim analysis due to lower mortality in the intervention group. There was significantly lower all-cause 28-day mortality in EDGT with ScvO2 than without ScvO2 group [37.3% vs. 57.5%, adjusted hazard ratio 0.57, 95%CI 0.33 to 0.97, P=0.04]. Therapeutic endpoints were achieved early in 'with' ScvO2 group [mean (SD) 3.6 (1.6) vs. 4.2 (1.6) h, P=0.03]. Organ dysfunction by sequential organ assessment score during PICU stay was lower in 'with' ScvO2 group [median (IQR) 5 (2,11) vs. 8 (3,13); P=0.03]. There was no significant difference in other secondary outcomes. CONCLUSIONS: EGDT with intermittent ScvO2 monitoring was associated with reduced mortality and improved organ dysfunction in pediatric septic shock.

A Prospective Cohort Study on Serum Sodium and Clinical Outcome in Pediatric Nontraumatic Coma.

OBJECTIVE: To study the serum sodium level and clinical outcome in pediatric nontraumatic coma. METHODS: A prospective cohort study was conducted in a tertiary care pediatric intensive care unit (PICU) from September 2015 to June 2016. Children aged < 13 y with nontraumatic coma [modified-Glasgow Coma Scale (m-GCS) score ≤ 8 or fall of ≥ 3 from baseline within 24 h of admission] were included. Children who received intravenous fluids for > 24 h, those with developmental delay, or died within 24 h of admission were excluded. The serum sodium profile (mEq/L) in the first 72 h and clinical outcome [mortality, length of stay in mechanical ventilation, PICU, and hospital] were studied. RESULTS: Eighty patients [Died n = 26 and Survived n = 54] were enrolled. Median [interquartile range (IQR)] age and m-GCS were 21 (4-78) mo and 9 (7-11), respectively. The mean [standard deviation (SD)] Pediatric Risk of Mortality-III (PRISM-III) was 17.7 (4). The most common etiology was acute central nervous system (CNS) infections (30%, n = 24) followed by an intracranial bleed (11.3%, n = 9). Mean (Standard error, SE) sodium levels and fluctuation of serum sodium from baseline up to 72 h were similar between nonsurvivors and survivors [140.8 (1.3) vs. 139.6 (0.8), p = 0.421] and [1.2 (0.3) vs. 0.8 (0.2), p = 0.307], respectively. On multivariate analysis, the need for vasoactive therapy was an independent predictor of mortality [adjusted odds ratio = 20.78, 95% CI 4.24-101.85, p = < 0.001, R2 = 0.62]. CONCLUSION: Mean serum sodium within normal range and fluctuation of serum sodium of 0.8 to 1.2 mEq/L over 72 h was not associated with poor outcomes in pediatric nontraumatic coma. Vasoactive therapy was an independent predictor of mortality.

Trial of Furosemide to Prevent Acute Kidney Injury in Critically Ill Children: A Double-Blind, Randomized, Controlled Trial.

OBJECTIVE: To study whether furosemide infusion in early-onset acute kidney injury (AKI) in critically ill children would be associated with a reduced proportion of patients progressing to the higher stage (Injury or Failure) as compared to placebo. METHOD: A double-blind, placebo-controlled, randomized pilot trial was conducted. The authors enrolled children aged 1-mo (corrected) to 12-y, who were diagnosed with AKI ("risk" stage) using pediatric-Risk, Injury, Failure, Loss, End stage kidney disease (p-RIFLE) criteria, and achieved immediate resuscitation goals within 24 h of admission. Participants received either furosemide (0.05 to 0.4 mg/kg/h) or placebo (5%-dextrose) infusion. The primary outcome was the proportion of patients progressing to a higher stage (injury or failure). Secondary outcomes were (i) need for renal replacement therapy, (ii) the effect on neutrophil gelatinase-associated lipocalin (urine and blood), (iii) fluid balance, (iv) adverse effects, (v) time to achieve renal recovery, (vi) duration of hospital stay and mechanical ventilation, and (vii) all-cause 28-d mortality. RESULTS: The trial was stopped for futility, and data were analyzed on an intention-to-treat basis (furosemide-group: n = 38; placebo-group: n = 37). No significant difference was noted in the progression of AKI to a higher stage between furosemide and placebo groups (10.5% vs. 21.6%; relative risk = 0.49, 95% CI 0.16 to 1.48) (p = 0.22). There were no differences in the secondary outcomes between the study groups. All-cause 28-d mortality was similar between the groups (10.5% vs. 10.8%). No trial-related severe adverse events occurred. CONCLUSIONS: Furosemide infusion in early-onset AKI did not reduce the progression to a higher stage of AKI. A future trial with large sample size is warranted.

Prospective Inverse Probability of Treatment-Weighting Analysis of the Clinical Outcome of Red Blood Cell Transfusion Practice in Critically Ill Children.

OBJECTIVE: To study the clinical outcomes of red blood cell (RBC) transfusion practices in critically ill children. METHOD: This prospective cohort study was conducted in a tertiary care pediatric intensive care unit (PICU) from March-2015 to January-2018. Inverse probability of treatment weighting (IPTW) using propensity score analysis was used. Children aged 1 mo to 12 y admitted to the PICU were screened. Patients were classified into 'transfused' and 'nontransfused', based on whether they received a transfusion or not. Patients with hematological malignancies, or immunosuppressant drugs, or those who received repeated transfusions, or received transfusion before admission, or died within 24 h were excluded. The primary outcome was all-cause 28 d mortality. Secondary outcomes were new-onset organ dysfunction, mechanical ventilation duration, and length of PICU and hospital stay. RESULTS: A total of 1014 patients [transfused = 277; nontransfused = 737) were included. In IPTW analysis, the risk of all-cause 28 d mortality was 53% higher in transfused than nontransfused patients [hazard ratio = 1.53, 95% CI: 1.18-1.98, p = 0.001 by Log-rank test]. Organ dysfunction was higher in transfused than nontransfused patients [3.8% vs. 1.3%, hazard ratio = 3.0, 95% CI: 1.40-6.48, p = 0.005]. The risk of staying in the mechanical ventilation was similar in both groups [hazard ratio = 1.03, 95% CI: 0.86-1.23, p = 0.756]. The risk of extended stay in the PICU and hospital was 16% and 21% higher in transfused than nontransfused patients [hazard ratio = 1.16, 95% CI: 1.03-1.30; p = 0.005; and 1.21, 95% CI: 1.08-1.36; p = 0.001], respectively. CONCLUSION: Red blood cell transfusion was independently associated with higher all-cause 28 d mortality and morbidities in critically ill children.

Low-Dose (0.05 Unit/kg/hour) vs Standard-Dose (0.1 Unit/kg/hour) Insulin in the Management of Pediatric Diabetic Ketoacidosis: A Randomized Double-Blind Controlled Trial.

OBJECTIVE: To compare the efficacy of insulin infusion of 0.05 Unit/kg/hour vs 0.1 Unit/kg/hour in the management of pediatric diabetic ketoacidosis (DKA). DESIGN: Randomized, double-blind controlled clinical trial. SUBJECT: Pediatric critical care division of a tertiary care hospital from October, 2014 to July, 2018. PARTICIPANTS: Children aged 12 years or younger with a diagnosis of DKA. Children with septic shock and those who had received insulin before enrollment were excluded. INTERVENTION: Low-dose (0.05 Unit/kg/hour) vs. Standard-dose (0.1 Unit/kg/hour) insulin infusion. OUTCOME MEASURES: The primary endpoint was time for resolution of DKA (pH ≥7.3, bicarbonate ≥15 mEq/L, beta-hydroxybutyrate <1 mmol/L). Secondary outcomes were the rate of fall in blood glucose until 250 mg/dL or less and the rate of complications (hypokalemia, hypoglycemia, and cerebral edema). RESULTS: Sixty patients were analyzed on an intention-to-treat basis (Low-dose group: n=30; Standard-dose group: n=30). Mean (SD) time taken for the resolution of ketoacidosis was similar in both groups [22 (12) vs 23 (18.5) hours; P=0.92]. The adjusted hazard ratio (95% CI) of the resolution of ketoacidosis was lower in the low-dose group [0.40 (0.19 to 0.85); P=0.017]. Mean (SD) rate of blood glucose decrease until 250 mg/dL or less reached [56 (41) vs 64 (65) mg/dL/hour; P=0.41] and time to achieve the target [4.2 (3.1) vs 4.8 (3.3) hours; P=0.44] were similar in both groups. Hypokalemia [30% vs 43.3%; P=0.28] and hypoglycemia [3.3% vs 13.3%; P=0.35] were lower in low-dose group. No child had cerebral edema, and no mortality occurred. CONCLUSIONS: Time for resolution of ketoacidosis was similar in the low-dose and standard-dose insulin with a lower rate of therapy-related complications in the low-dose group. Hence, low-dose insulin infusion can be a safer approach in the management of pediatric DKA.

Epinephrine Plus Vasopressin vs Epinephrine Plus Placebo in Pediatric Intensive Care Unit Cardiopulmonary Resuscitation: A Randomized Double Blind Controlled Clinical Trial.

OBJECTIVE: To compare the efficacy of epinephrine plus vasopressin vs epinephrine plus placebo in the pediatric intensive care unit (PICU) cardiopulmonary resuscitation (CPR). DESIGN: Randomized, double-blind controlled clinical trial. SETTING: PICU in a tertiary care institute from February, 2019 to May, 2020. PARTICIPANTS: Children aged one month to 13 years who required CPR during PICU stay. Patients in whom vascular access was not available or return of spontaneous circulation (ROSC) was achieved by defibrillation without epinephrine were excluded. INTERVENTION: Patients were randomized to receive vasopressin 0.1 mL per kg (=0.8 unit per kg) or placebo (0.1 mL per kg normal saline) in addition to epinephrine (1:10000) 0.1 mL per kg. The drugs were given as bolus doses every three minutes until the ROSC or up to a maximum of five doses, whichever was earlier. OUTCOME MEASURE: The primary outcome was the proportion of patients who achieved ROSC. The secondary outcomes were survival rate and functional status (at 24-hour, PICU, hospital, and 90-day post-discharge), need for organ supports, length of stay (PICU and hospital), and adverse effect(s) of the study drugs. RESULTS: 90 patients (epinephrine plus vasopressin group, n=45 and epinephrine plus placebo group, n=45) were analyzed on intention-to-treat basis. There was no significant difference in the primary outcome between epinephrine plus vasopressin (n=25, 55.5%) and epinephrine plus placebo groups (n=24, 53.3%) (Relative risk 1.04, 95% CI 0.71 to 1.52). There was no significant difference in survival rate at 24-hour (n=7, 15.6% vs. n=8, 17.8%), at PICU, hospital, and 90-day post-discharge (n=1, 2.2% vs n=1, 2.2%). There was no difference in other secondary outcomes. No trial drug-related serious adverse events were observed. CONCLUSIONS: A combination of epinephrine plus vasopressin did not improve the rate of return of spontaneous circulation in the pediatric intensive care unit cardiopulmonary resuscitation as compared with epinephrine plus placebo.

Retrospective Hospital-Based Cohort Study on Risk Factors of Poor Outcome in Pediatric Snake Envenomation.

BACKGROUND AND OBJECTIVES: Among Southeast Asian countries, India has reported the highest mortality due to snakebite envenomation. To identify the risk factors of poor outcome (mortality/mechanical ventilation/renal replacement therapy-RRT) in pediatric snakebite envenomation. METHOD: Case records of children aged less than 13 years with snakebite envenomation admitted between June 2009 and July 2015 were reviewed retrospectively. Medical records of the patient died within 6 h, those required RRT before administration of antisnake venom (ASV), and those with unknown bites were excluded. RESULTS: A total of 308 patients were included. One hundred eighty (58.4%) had hemotoxic, and 128 (41.6%) had neuroparalytic envenomation. Median (interquartile range) bite to ASV time was 3 (2-6) h. Seventy-five (24.4%) patients received ASV within 6 h of bite. Poor outcomes occurred in 128 (41.6%), and 36 (11.7%) patients died. On binary logistic analysis (adjusted odds ratio, 95% confidence interval), age ≤5 years (2.97, 1.28-6.90), walking (6.15, 2.88-13.17), playing (3.36, 1.64-6.88), no tourniquet (2.39, 1.25-4.57), time to ASV more than 6 h (2.71, 1.45-5.06), fang marks (2.22, 1.21-4.07), neurotoxic envenomation (3.01, 1.11-8.13) and additional ASV dose (8.41, 2.99-23.60) were independently predicted the poor outcome (Hosmer and Lemeshow goodness of fit model p = 0.135; overall percentage of the model is 72.2% and R-square = 0.28). CONCLUSION: Age below 5 years, activity at/after the bite (playing/walking), no tourniquet, a longer bite to ASV time, presence of fang marks, neurotoxic envenomation and need for additional ASV dose were independent predictors of poor outcome in pediatric snakebite envenomation.

Incidence, Risk Factors, the Role of Plasma NGAL and Outcome of Contrast-Induced Acute Kidney Injury in Critically Ill Children.

OBJECTIVES: To study the incidence of contrast-induced acute kidney injury (CI-AKI), evaluate its risk factors, study the role of plasma neutrophil gelatinase-associated lipocalin (NGAL) and evaluate the outcome of CI-AKI in critically ill children. METHODS: In this prospective cohort study, children aged 1 mo to 12 y who underwent contrast computed tomography (CECT) for various medical indications were included. Patients without renal function test before contrast administration, children with chronic kidney disease, children admitted for less than 48 h, and those with serum bilirubin more than 5 mg per dL were excluded. Serum creatinine and estimated-Glomerular filtration rate (e-GFR) were measured at admission, immediately before, and at 6, 24, 48 h after contrast. Plasma neutrophil gelatinase-associated lipocalin (NGAL) was measured before and 6 h after contrast. The incidence of CI-AKI by p-RIFLE (Pediatric Risk, Injury, Failure, Loss, End Stage Renal Disease) criteria, its risk factors, the diagnostic role of NGAL in CI-AKI, and outcomes [30 d unfavorable outcome (death, readmission) and renal recovery] were studied. RESULTS: One hundred children were enrolled. The indications for CECT were brain (58%) and respiratory pathology (20%). Incidence of CI-AKI was 35% (95% CI 26.4% to 44.8%); 71% in 'Risk,' and 29% in the 'Injury' stage. After multivariate logistic regression, age younger than 2 y was independently associated with CI-AKI. There was no significant difference in NGAL before (ROC-AUC 0.38, 95% CI 0.26 to 0.50) and 6 h after CECT scan (AUC 0.41, 95% CI 0.29 to 0.54) to predict CI-AKI. There were 7% deaths but no readmission at 30 d. Among 33 CI-AKI patients who survived, the operational definition of renal recovery was achieved in 51.5% (n = 17), complete renal recovery was achieved in 97% (n = 32), and partial renal recovery was achieved in 3% (n = 1) of patients at discharge, while none received renal supportive therapy. CONCLUSIONS: The incidence of contrast-induced acute kidney injury was 35% with age younger than two year being independently associated with CI-AKI. NGAL did not predict the CI-AKI.

Use of Honey Versus Standard Care for Hospital-Acquired Pressure Injury in Critically Ill Children: A Multicenter Randomized Controlled Trial.

OBJECTIVES: To examine if the use of honey (medicated) for dressing is superior to standard care in terms of time to complete wound healing in stages 1-3 of pressure injuries in children admitted to the PICU. DESIGN: Multicenter, open-label, parallel-group, randomized trial. SETTING: Tertiary-care PICU from August 2017 to January 2019. PATIENTS: Critically ill children, 2 months to 17 years old, who developed pressure injury (stages 1-3) were included; those on more than two inotropes or with signs of acute wound infection or wounds with greater than 5 cm diameter or known allergy to honey were excluded. INTERVENTIONS: Children were randomized to receive either medicated honey dressing or standard (routine) wound care for the management of their pressure injury. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the time to complete wound healing. Manuka or active Leptospermum honey dressing/gel was used in the intervention group. Enrolled children were followed up until death or discharge from the hospital. A total of 99 children were enrolled: 51 in the intervention group and 48 in the standard care group. Baseline characteristics, including the nutritional status, were comparable between the groups. The most common sites of injury were bony prominences at face mask contact points. The median time to complete healing was 7 days (95% CI, 6-7 d) versus 9 days (7-10 d) in the intervention and standard care groups, respectively (p = 0.002; log-rank test). At any random time, children in the intervention group were about 1.9-fold more likely to have their pressure injury completely healed than those in the standard care group (hazard ratio 1.86; 95% CI, 1.21-2.87). There were no allergic reactions or secondary wound infections in the intervention group. CONCLUSIONS: The use of medicated honey dressings decreased the time to wound healing in critically ill children with pressure injuries. There were no allergic reactions or secondary bacterial infections in any of these children.

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.