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.

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.

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.

Randomized Double-blind Trial of Ringer Lactate Versus Normal Saline in Pediatric Acute Severe Diarrheal Dehydration.

OBJECTIVE: The aim of this study was to compare the effectiveness of Ringer lactate (RL) versus normal saline (NS) in the correction of pediatric acute severe diarrheal dehydration, as measured by improvement in clinical status and pH (≥7.35). METHODS: A total of 68 children ages 1 month to 12 years with acute severe diarrheal dehydration (World Health Organization [WHO] classification) were randomized into RL (n = 34) and NS groups (n = 34) and received 100 mL/kg of the assigned intravenous fluid according to WHO PLAN-C for the management of diarrheal dehydration. The primary outcome was an improvement in clinical status and pH (≥7.35) at the end of 6 hours. Secondary outcomes were changes in serum electrolytes, renal and blood gas parameters, the volume of fluid required for dehydration correction excluding the first cycle, time to start oral feeding, hospital stay, and cost-effectiveness analysis. RESULTS: Primary outcome was achieved in 38% versus 23% (relative risk = 1.63, 95% confidence interval 0.80-3.40) in RL and NS groups, respectively. No significant differences were observed in secondary outcomes in electrolytes, renal, and blood gas parameters. None required second cycle of dehydration correction. Median (interquartile range) time to start oral feeding (1.0 [0.19-2.0] vs 1.5 [0.5-2.0] hours) and hospital stay (2.0 [1.0-2.0] vs 2.0 [2.0-2.0] days) was similar. The median total cost was higher in RL than NS group ((Equation is included in full-text article.)120 [(Equation is included in full-text article.)120-(Equation is included in full-text article.)180] vs (Equation is included in full-text article.)55 [(Equation is included in full-text article.)55-(Equation is included in full-text article.)82], P ≤ 0.001). CONCLUSION: In pediatric acute severe diarrheal dehydration, resuscitation with RL and NS was associated with similar clinical improvement and biochemical resolution. Hence, NS is to be considered as the fluid of choice because of the clinical improvement, cost, and availability.

Histopathological changes in septic acute kidney injury in critically ill children: a cohort of post-mortem renal biopsies.

BACKGROUND: Septic acute kidney injury (AKI) accounts for more than half of all cases of AKI in critically ill children. The renal histology was found to alter the management in more than two-third of cases of adult acute renal failure. Better insight into the pathogenesis of pediatric septic AKI could be based on developing a clearer appreciation of the histopathological changes. No comprehensive study of the histopathological features of septic AKI in critically ill children has yet been performed. METHODS: This retrospective observational study was conducted at a level-III pediatric intensive care unit (PICU) from June 2013 to July 2014. Children (<13 years of age) who had expired due to sepsis and AKI and had post-mortem renal biopsies were included. Sepsis and AKI were defined according to the International pediatric sepsis consensus conference and Acute Kidney Injury Network (AKIN) definition and classification system, respectively. RESULTS: A total of 708 patients were admitted to the PICU during the study period, with mortality of 24 % (n = 170) and 62 complete data of post-mortem renal biopsies were included. The median (IQR) age was 12 (4.8-36) months, pediatric risk of mortality score (PRISM) III was 14 (12-18) and the time to biopsy after death was 24 (18-26) minutes. Normal histology was the most common change 41.9 % (n = 26), followed by acute tubular necrosis (ATN) 30.6 % (n = 19). A combination of changes involving tubules, glomeruli, interstitium, and blood vessels was noted in 21 % (n = 13) of the specimens. Eight percent (n = 5) of the specimens had features consistent with thrombotic microangiopathy. Normal histology was noted in 15.4 % (n = 4/26), 50 % (n = 13/26), and 34.6 % (n = 9/26) of AKI stage-I, II, and III, respectively. CONCLUSION: The most common renal histopathological change in septic AKI in critically ill children was normal histology followed by ATN.

Koebner's Phenomenon in Childhood Henoch-Schönlein Purpura: A Report of Two Cases.

Koebner's phenomenon occurs rarely in connection with Henoch-Schönlein purpura (HSP). We report two children with HSP who developed Koebner's phenomenon on the second day after the onset of rash. The first was an 11-year-old girl with rheumatic heart disease who presented with abdominal pain for 1 month and subsequently developed rash and nephritis. The second patient was a 7-year-old girl who presented with rash and polyarthritis. To the best of our knowledge, Koebner's phenomenon in childhood HSP has not been reported.

N-acetylcysteine in Cleistanthus collinus Poisoning: A Report of Two Cases in Children.

Cleistanthus collinus, also known as Oduvanthalai in Tamil, is the most commonly encountered plant poison in southern India. The leaves are used for poisoning humans (suicide or homicide) and animals (cattle and fish) and as an abortifacient, especially in rural south India. Although this poisoning is commonly reported in adults, data regarding the use of N-acetylcysteine in pediatric poisoning is lacking. We report two previously healthy male siblings of pediatric age group who ingested the liquid extracted from crushed leaves of this plant given to them by their mother as a means of deliberate harm. Both patients developed distal renal tubular acidosis, with hypokalemia. The younger sibling also developed myocardial toxicity. Other significant findings noted include hypocalcemia, hypomagnesemia and elevated liver enzymes. Both patients received supportive care along with N-acetylcysteine infusion, and showed complete recovery within 10 days.

Immunoglobulin A nephropathy in association with generalized inflammatory peeling skin syndrome.

We describe an 8-year-old girl born to second-degree consanguineous parents with complaints of recurrent episodes of hematuria for 6 months. She had generalized peeling of the skin since birth and recurrent purulent cutaneous infections. The clinical presentation and histopathology of the skin biopsy specimen were consistent with the inflammatory variant of peeling skin syndrome (PSS). She also had a single ventricle with pulmonary stenosis, for which a bidirectional Glenn shunt had been placed. The renal biopsy specimen showed immunoglobulin A (IgA) nephropathy. She responded well to enalapril and steroids, with a decrease in proteinuria. IgA nephropathy has not been previously reported in PSS. Complications such as IgA nephropathy in children with PSS would help to further delineate the diverse clinical presentations and the clinical course of this rare dermatosis. We discuss the mechanisms that could explain this hitherto unreported association.

Acitretin-responsive ichthyosis in Chanarin-Dorfman syndrome with a novel mutation in the ABHD5/CGI-58 gene.

Chanarin-Dorfman syndrome (CDS) is a rare nonlysosomal neutral lipid storage disorder characterized by congenital ichthyosis, lipid vacuoles in leukocytes (Jordan's anomaly), and hepatomegaly. The authors herein report an 18-month-old boy with ichthyosis and hepatomegaly diagnosed with CDS and confirmed to have a novel c.506-3C>G mutation in the ABHD5/CGI-58 gene. Our case also illustrates that retinoids such as acitretin could be useful in the treatment of skin manifestations in CDS even in the presence of liver derangement.

Clinical profile of acute kidney injury in a pediatric intensive care unit from Southern India: A prospective observational study.

BACKGROUND: Although the term acute renal failure was replaced by acute kidney injury (AKI) recently, there is a paucity of data on the incidence and profile of AKI in critically ill children from the developing world. OBJECTIVES: The objective of this study is to determine the incidence, etiology, short term outcome and predictors of fatality in critically ill children admitted to the pediatric intensive care unit (PICU) with AKI, aged 1 month to 13 years. MATERIALS AND METHODS: In this prospective observational study, from June 2010 to March 2011, 215 children admitted to the PICU were screened for AKI, defined according to the AKI Network criteria. The patients with AKI were followed-up until discharge/death. Their clinical and biochemical data were recorded. RESULTS: The incidence of AKI among 215 patients screened was 54 (25.1%). The common etiologies were infections, [34 (62.9%)], acute glomerulonephritis (7.6%), snake envenomation (5.7%), hemolytic uremic syndrome (3.8%) and congestive cardiac failures (3.8%). Among infections, pneumonia and septicemia constituted 26.5% each, meningoencephalitis accounted for 23.5%, and dengue, scrub typhus, tuberculosis and malaria constituted 9.3% of children with AKI. 27.8% of patients required dialysis. Overall mortality was 46.3%. On logistic regression analysis, requirement of mechanical ventilation was an independent predictor of fatality in AKI. CONCLUSIONS: Besides the high incidence of AKI in critically ill-children admitted to the PICU (25.1%), the condition was associated with adverse outcomes, including high mortality (46.3%) and need for dialysis (27.8%). Infections dominated the etiological profile. Requirement of mechanical ventilation predicted an adverse outcome in our patient population.

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.

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.

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.

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.

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.

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.