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.

Normal Anion Gap Metabolic Acidosis in Pediatric Acute Diarrhea: A Menace or an Innocent Bystander?

How to cite this article: Bhowmick R. Normal Anion Gap Metabolic Acidosis in Pediatric Acute Diarrhea: A Menace or an Innocent Bystander? Indian J Crit Care Med 2022;26(12):1235-1236.

Pediatric Acute Respiratory Distress Syndrome in COVID-19 Pandemic: Is it the Puzzle of the Century?

Bhowmick R, Gulla KM. Pediatric Acute Respiratory Distress Syndrome in COVID-19 Pandemic: Is it the Puzzle of the Century? Indian J Crit Care Med 2022;26(3):264-265.

Endotracheal Tube Cuff Pressure Monitor: A Fancy Gadget or Necessary Tool in Intensivist's Armamentarium.

How to cite this article: Bhowmick R. Endotracheal Tube Cuff Pressure Monitor: A Fancy Gadget or Necessary Tool in Intensivist's Armamentarium. Indian J Crit Care Med 2021;25(2):121-122.

Anterolateral thigh measurements by ultrasound in neonates and young infants to ensure safe intramuscular injections during vaccination in low- and middle-income countries.

BACKGROUND: Use of same length needle for intramuscularly administered vaccines had been reported to cause under-and over-penetration among infants due to their different body weights and underlying variations in the fat and muscle thickness. Normative data regarding thigh compartment thickness are, however, lacking among neonates and infants aged ≤12 weeks particularly in low- and middle-incoming countries with high burden of low birth weight/growth restricted infants. METHODS: Present study investigated skin to muscle and skin to bone (STBD) distances of anterolateral thigh of babies (n = 300) aged ≤12 weeks (1-80 days) with different weight groups (<3 kg, 3-4 kg and >4 kg) by ultrasonography during their intramuscular vaccinations. RESULTS: Overall, mean [standard deviation (SD)] STBD was 17.04 (2.66) mm with range of 10.60-23.30 mm. Stratifying by current body weight, mean (SD) STBD in infants weighing less than 3 kg was 14.39 (1.23) mm. For infants weighing between 3-4 kg and >4 kg, the mean (SD) STBD were 16.69 (1.43) mm and 17.04 (2.66) mm, respectively. Estimated safety (no risk of over-penetration) of 16 mm was observed in 57.33% (172) infants whereas 25 mm needle had 100% over-penetration risk in the study cohort. Current body weight of infants was a significant predictor of safe injection [area under the receiver operating characteristic (ROC) curve 0.95; 95% CI 0.92-0.97]. CONCLUSIONS: Our study offers objective normative measurements of anterolateral thigh for safe intramuscular vaccination in young infants especially for low birth weight and growth restricted infants in low- and middle-income countries.

Clinical Profile and Outcomes of Children with Acute Liver Failure in a Tertiary Care Center in South India: A Retrospective Study.

Purpose: In this study, we investigated the clinical profile, survival at discharge, and proportion of children with acute liver failure (ALF) meeting the criteria for, yet surviving without, liver transplantation (LT). Methods: Medical case records of children aged >28 days to ≤15 years over a period of 7 years, identified from pediatric admission and discharge registers, were screened. Children satisfying the criteria for ALF were included in this study. Results: A total of 71 records meeting the pediatric ALF (PALF) criteria were included. The survival rate at discharge was 61% (n=44). A considerable proportion of children satisfied the King's College Criteria (KCC) (56.3%) and the European Association for the Study of the Liver (EASL) criteria (7%) for LT at admission. Nonetheless, the survival rate in the absence of LT was 42.5% in children who satisfied the KCC and 20% in those who met the EASL criteria. Infection (29.5%) and paracetamol overdose (19.7%) were the major identifiable causes of PALF. Hepatitis A was the most common infection identified. No significant predictors of poor outcomes were identified in multivariable analysis. Conclusion: Our study highlights the changing survival rates and the clinical and etiological profiles of patients with PALF. In areas with poor access to LT services, survival in these children could be improved through early referral to centers with adequate intensive care facilities. Preventing ALF and referring patients to LT services are paramount to reducing mortality.

A Rapid and Scalable Multiplex PCR-Based Next-Generation Amplicon Sequencing Method for Familial Hypercholesterolemia Genetic Screening.

BACKGROUND: Familial hypercholesterolemia (FH) is a frequently underdiagnosed genetic disorder characterized by elevated low-density lipoprotein (LDL) levels. Genetic testing of LDLR, APOB, and PCSK9 genes can identify variants in up to 80% of clinically diagnosed patients. However, limitations in time, scalability, and cost have hindered effective next-generation sequencing of these genes. Additionally, pharmacogenomic variants are associated with statin-induced adverse effects in FH patients. To address these challenges, we developed a multiplex primer-based amplicon sequencing approach for FH genetic testing. METHODS: Multiplex primers were designed for the exons of the LDLR, APOB, and PCSK9 genes, as well as for pharmacogenomic variants rs4149056 (SLCO1B1:c.521T > A), rs2306283 (SLCO1B1:c.388A > G), and rs2231142 (ABCG2:c.421C > A). Analytical validation using samples with known pathogenic variants and clinical validation with 12 FH-suspected probands were conducted. Library preparation was based on a bead-based tagmentation method, and sequencing was conducted on the NovaSeq 6000 platform. RESULTS: Our approach ensured no amplicon dropouts, with over 100× coverage on each amplicon. Known variants in 2 samples were successfully detected. Further, we identified one heterozygous LDLR (p.Glu228Ter) variant and 2 homozygous cases of LDLR (p.Lys294Ter) and LDLR (p.Ser177Leu) variants in patients. Pharmacogenomic analysis revealed that overall 3 patients may require reduced statin doses. Our approach offered reduced library preparation time (approximately 3 h), greater scalability, and lower costs (under $50) for FH genetic testing. CONCLUSIONS: Our method effectively sequences LDLR, APOB, and PCSK9 genes including pharmacogenomic variants that will guide appropriate screening and statin dosing, thus increasing both efficiency and affordability.

A rare case of metapneumovirus-induced rhabdomyolysis and multi-organ dysfunction in a 4-year-old child.

Human metapneumovirus (hMPV) is a common cause of acute respiratory tract infections in children. In immunocompetent individuals, the course of hMPV infection is usually benign and self-limiting. A developmentally normal, previously healthy 4-year-old girl presented with pneumonia and later developed rhabdomyolysis and multi-organ dysfunction syndrome (MODS) which was fatal. Extensive microbiological investigation for a possible viral aetiology was positive only for hMPV, thus making it the first reported case of hMPV infection-related rhabdomyolysis.Abbreviations: ARDS, acute respiratory distress syndrome; CK, creatinine kinase; hMPV, human metapneumovirus; MODS, multi-organ dysfunction syndrome; RSV, respiratory syncytial virus.

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.

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.

Kinetic Estimated Glomerular Filtration Rate and Severity of Acute Kidney Injury in Critically Ill Children.

OBJECTIVE: To study the Kinetic estimated Glomerular Filtration Rate (KeGFR) using serum creatinine (SCr) for the identification of acute kidney injury (AKI), stages of AKI, and extent of agreement with Kidney Disease Improving Global Outcomes (KDIGO) classification in critically ill children. METHODS: A prospective observational study was conducted in a pediatric intensive care unit (PICU) in a tertiary care institute of South India from July through August 2018. Sixty children were enrolled. The patients with known End-Stage Renal Disease (ESRD), with previous renal transplantation, admission SCr more than 4 mg per dL, expired within 24 h of admission and patients who underwent Renal Replacement Therapy (RRT) before PICU admission were excluded. KeGFR was calculated for the first seven days, and the worst achieved value was determined. AKI staging by KDIGO was compared with AKI by KeGFR value. The requirement of RRT, multi-organ dysfunction syndrome (MODS), mechanical ventilation, cumulative fluid balance, PICU stay, and hospital mortality was recorded. RESULTS: AKI detection by KeGFR method showed a sensitivity of 93% (95% CI 80% - 98.2%) and specificity of 76% (95% CI 49.8% - 92.2%) compared to KDIGO criteria. The good agreement between KDIGO and KeGFR values for AKI was noted (Kappa = 0.71, p < 0.001). It was observed that 81.3% (n = 13) of Group-I, 56% (n = 14) of Group-II, 77.8% (n = 7) of Group-III and 90% (n = 9) of Group-IV by KeGFR were graded as Stage-0, Stage-1, Stage-2 and Stage-3 of AKI by KDIGO criteria respectively (p < 0.001). There was no significant difference noted in secondary outcomes. The survival of children with AKI and those without AKI (by both KDIGO staging and KeGFR) showed no significant difference. CONCLUSIONS: KeGFR is highly sensitive, and there is a good agreement with KDIGO criteria in the identification of AKI in critically ill children. Further research is required to validate these study results.

Does severe ADAMTS13 deficiency in thrombotic microangiopathy rule out complement-mediated atypical hemolytic uremic syndrome.

In evaluating a patient with thrombotic microangiopathy (TMA), it is necessary to rule out thrombotic thrombocytopenic purpura before a diagnosis of atypical hemolytic uremic syndrome (aHUS) is made. There have been reports that mutations of complement factors can coexist with partial A Disintegrin and Metalloproteinase with a ThromboSpondin type 1 motif, member 13 deficiency. Here, we report the case of a 6-year-old girl who was initially diagnosed as nephrotic syndrome and developed TMA after five years of onset of illness. She had poor response to treatment and had multiple relapses due to associated complement factor mutation. Hence, genetic evaluation has to be considered in all children presenting with aHUS.