Role of next generation sequencing in diagnosis and management of critically ill children with suspected monogenic disorder.

Next generation sequencing based diagnosis has emerged as a promising tool for evaluating critically ill neonates and children. However, there is limited data on its utility in developing countries. We assessed its diagnostic rate and clinical impact on management of pediatric patients with a suspected genetic disorder requiring critical care. The study was conducted at a single tertiary hospital in Northern India. We analyzed 70 children with an illness requiring intensive care and obtained a precise molecular diagnosis in 32 of 70 probands (45.3%) using diverse sequencing techniques such as clinical exome, whole exome, and whole genome. A significant change in clinical outcome was observed in 13 of 32 (40.6%) diagnosed probands with a change in medication in 11 subjects and redirection to palliative care in two subjects. Additional benefits included specific dietary management (three cases), avoidance of a major procedure (one case) and better reproductive counseling. Dramatic therapeutic responses were observed in three cases with SCN1A, SCN2A and KCNQ2-related epileptic encephalopathy. A delayed turn-around for sequencing results was perceived as a major limiting factor in the study, as rapid and ultra-rapid sequencing was not available. Achieving a precise molecular diagnosis has great utility in managing critically ill patients with suspected genetic disorders in developing countries.

Indigenous Bubble Continuous Positive Airway Pressure for Children.

How to cite this article: Gupta D, Simalti AK. Indigenous Bubble Continuous Positive Airway Pressure for Children. Indian J Crit Care Med 2023;27(11):788-789.

Flexible Fiberoptic Bronchoscopy in Non-ventilated Children in Pediatric Intensive Care Unit: Utility, Interventions and Safety.

Objective: To study the utility of flexible fiberoptic bronchoscopy (FFB), and its effects on oxygenation and hemodynamics in children while on respiratory assist devices. Materials and methods: The data of non-ventilated patients who underwent FFB during their stay in the PICU from January 2012 to December 2019 was retrieved from medical, nurses, and bronchoscopy records. The study parameters, demography, diagnosis, indication, and findings of FFB and interventions done after FFB, were noted, and also the oxygenation and hemodynamic parameters before, during and 3 hours after FFB. Results: Data from the first FFB of 155 patients were analyzed retrospectively. About 54/155 (34.8%) children underwent FFB while on HFNC. About 75 (48.4%) patients were on conventional oxygen therapy (COT) before FFB. There were 51 (33%) patients who had received mechanical ventilation and were extubated successfully. The 98 (63.2%) children had primary respiratory diseases. Stridor and lung atelectasis were indications for FFB in 75 (48.4%) cases and the commonest bronchoscopic finding was retained secretions in the airways. Based on the FFB findings, 50 medical and 22 surgical interventions were done. The commonest medical and surgical interventions were changes in antibiotics (25/50) and tracheostomy (16/22) respectively. There was a significant fall in SpO2 and a rise in hemodynamic parameters during FFB. All these changes were reversed after the procedure with no consequences. Conclusion: Flexible fiberoptic bronchoscopy is a useful tool to diagnose and guide interventions in non-ventilated pediatric intensive care unit (PICU). There were significant but transient changes in oxygenation and hemodynamics with no serious consequences. How to cite this article: Sachdev A, Gupta N, Khatri A, Jha G, Gupta D, Gupta S, et al. Flexible Fiberoptic Bronchoscopy in Non-ventilated Children in Pediatric Intensive Care Unit: Utility, Interventions and Safety. Indian J Crit Care Med 2023;27(5):358-365.

Indication-based timing of tracheostomy and its effects on outcome in the pediatric intensive care unit.

OBJECTIVES: The objective of study was to find an association between the timing of tracheostomy with duration of mechanical ventilation (MV) and length of stay (LOS) in pediatric intensive care unit (PICU) and hospital. METHODS: The data were collected prospectively from 2000 to 2018 and were analyzed retrospectively. Data included clinical diagnosis, indication, and duration (days) of MV, LOS in PICU and hospital before and after tracheostomy. Patients who did not receive MV or underwent MV for <24 h were excluded. According to the indication of tracheostomy enrolled patients were divided into four groups-airways anomalies (AA), central neurological impairment (CNI), cardiopulmonary insufficiency (CPI), and neuromuscular disorders (NMD). Patients in each group were divided into early (ET) and late tracheostomy (LT) category based on the median (interquartile range interquartile range [IQR]) days of pretracheostomy MV. RESULTS: Two hundred and fifty six patients were analyzed. The frequency and median [IQR] days of pretracheostomy MV were -AA 54 [7(3,16)], CNI 120 [12(9,16)], CPI 51 [25(16.5,30.5)], and NMD 31[12(8,16.5)]. In AA patients, median (IQR) durations of posttracheostomy MV [2(1,5.2) versus 3.5(2,12); p = 0.032], PICU [7(5,8.2) versus11(7,18); p = 0.004] and hospital [12(9.7,21) versus 21.5(12,28); p = 0.027] stays were lower in ET as compared with LT group. Posttracheostomy MV duration was significantly short in ET patients with CNI and NMD (p < 0.005). The total days of MV, PICU and hospital stay were significantly lower in ET as compared with LT patients in all four groups (p < 0.01). CONCLUSION: As compared with LT, ET patient had shorter durations of total MV and PICU and hospital stay.

COVID-19-associated Multisystem Inflammatory Syndrome in Children: A Multicentric Retrospective Cohort Study.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new entity affecting a small percentage of children during the COVID-19 pandemic. MATERIALS AND METHODS: Demography, clinical, and laboratory variables of children admitted from April to September 2020 with MIS-C were studied retrospectively at eight hospitals in Delhi, India. RESULTS: We identified 120 patients [median age: 7 years (interquartile range (IQR): 4-10)] with male-to-female ratio of 2.3:1. Overall, 73 out of 120 children (60.8%) presented with shock, 63 (52.5%) required inopressor support, and 51 (43%) required respiratory support. We categorized the cohort into three observed clinical phenotypes: MIS-C with shock (n = 63), MIS-C with Kawasaki disease (KD) (n = 23), and MIS-C without shock and KD (n = 34). Atypical presentations were hypothermia, orchitis, meningoencephalitis, demyelination, polyneuropathy, pancreatitis, and appendicitis. Ninety-four percent had laboratory evidence of SARS-CoV-2 (78.3%, seropositive and 15.8%, RT-PCR positive). The median C-reactive protein (CRP) was 136 mg/L (IQR, 63.5-212.5) and ferritin was 543 ng/mL (IQR, 225-1,127). More than 90% received immunomodulatory therapy (intravenous immunoglobulins and/or steroids) with an excellent outcome (96% survived). CRP and absolute neutrophil count (ANC) were correlated statistically with severity. CONCLUSION: MIS-C data from Delhi are presented. Rising CRP and ANC predict the severe MIS-C. HOW TO CITE THIS ARTICLE: Mehra B, Pandey M, Gupta D, Oberoi T, Jerath N, Sharma R, et al. COVID-19-associated Multisystem Inflammatory Syndrome in Children: A Multicentric Retrospective Cohort Study. Indian J Crit Care Med 2021;25(10):1176-1182.

MIS-C is a Clinically Different Entity from Acute COVID-19 in Adults.

Mehra B, Aggarwal V, Kumar P, Gupta D, Kundal M, Kumar A, et al. MIS-C is a Clinically Different Entity from Acute COVID-19 in Adults. Indian J Crit Care Med 2021;25(8):954-955.

Tracheostomy in Pediatric Intensive Care Unit-A Two Decades of Experience.

AIM AND OBJECTIVE: To study the profile, indications, related complications, and predictors of decannulation and mortality in patients who underwent tracheostomy in the pediatric intensive care unit (PICU). MATERIALS AND METHODS: Retrospective analysis of prospectively collected data of tracheostomies was done on patients admitted at PICU. Demographics, primary diagnosis, indication of tracheostomy, and durations of endotracheal intubation, mechanical ventilation, and tracheostomy cannulation were recorded. The indication was recorded in one of the four categories-upper airway obstruction (UAO), central neurological impairment (CNI), prolonged mechanical ventilation, and peripheral neuromuscular disorders). RESULTS: Two hundred ninety cases were analyzed. UAO (42%) and CNI (48.2%) were main indications in the halves of the study period, respectively. Decannulation was successful in 188 (64.8%) patients. Seventy-seven percentage UAO patients were decannulated successfully [OR (odds ratio); 95% CI (confidence interval), 2.647; 1.182-5.924, p = 0.018]. Age <1 year (0.378; 0.187-0.764; p = 0.007), nontraumatic, noninfectious central neurological diseases (0.398; 0.186-0.855; p = 0.018), and malignancy (0.078; 0.021-0.298; p <0.001), durations of posttracheostomy ventilation (0.937; 0.893-0.983; p = 0.008), and stay in the PICU (0.989; 0.979-0.999; p = 0.029) were predictors of unsuccessful decannulation. There were 91 (31.4%) deaths. Age <1 year (2.39 (1.13-5.05; p = 0.02), malignancy (17.55; 4.10-75.11; p <0.001), durations of posttracheostomy ventilation (1.06; 1.006-1.10; p = 0.028), and hospital stay (1.007; 1.0-1.013; p = 0.043) were independent predictors of mortality. Indication of UAO favored survivor (0.24; 0.09-0.57; p <0.001). CONCLUSION: The indications for tracheostomy in children had changed over the years. Infancy, primary diagnosis, length of posttracheostomy ventilation, and stay in the PICU and hospital were independent predictors of decannulation and mortality. WHAT THIS ADDS: Similar to developed countries, the age at the time of tracheostomy and indication are changing. Inability to decannulate and mortality were associated with the age of a child at the time of tracheostomy, indication, medical diagnosis, and duration of postprocedure mechanical ventilation and stay in the hospital. HOW TO CITE THIS ARTICLE: Sachdev A, Chaudhari ND, Singh BP, Sharma N, Gupta D, Gupta N, et al. Tracheostomy in Pediatric Intensive Care Unit-A Two Decades of Experience. Indian J Crit Care Med 2021;25(7):803-811.

Early Predictors of Mortality in Children with Severe Dengue Fever: A Prospective Study.

OBJECTIVE: The aim of the study was to identify early predictors of mortality in children with severe dengue fever admitted to pediatric intensive care unit (PICU). MATERIALS AND METHODS: All consecutive children with laboratory-confirmed severe dengue fever were enrolled in this prospective observational study. Besides demographic data, disease severity and organ dysfunction scores, laboratory investigations and interventions are done in PICU were recorded and analyzed. RESULTS: During the study period of 42 months, 172 patients with dengue fever were admitted to PICU. A total of 78 (45.3%) patients with severe dengue fever were included and analyzed. There were 20 (25.6%) deaths. There were significant differences in disease severity and organ dysfunction scores, transaminases, blood lactate level and serum creatinine between survivors and nonsurvivors. A significantly higher number of nonsurvivors required interventions in first 24 hours of admission. Platelet counts (P value 0.22) and hematocrit (P value 0.47) were not statistically different in 2 groups. There was a significantly high vasopressor-inotrope score (VIS) (<0.001) and positive fluid balance >10% (0.002) in nonsurvivors. Multivariate stepwise logistic regression analysis identified serum glutamic pyruvic transaminases (≥ 284 IU/L; odds ratio [OR] 1.002, 95% confidence interval [CI]: 1.001-1.003), blood lactate level (≥2.73 mmol/L; OR 2.08, 95% CI: 1.354-3.202), Pediatric Risk of Mortality score at 12 hours (≥14.5; OR 1.35, 95% CI: 1.077-1.693), VIS (≥22.5, OR 1.129, 95% CI: 1.059-1.204) and positive fluid balance >10% (OR 22.937, 95% CI: 2.393-219.84) at 24 hours of admission as independent predictors of mortality. CONCLUSION: Disease severity, hyperlactatemia at admission, need for multiple vasoactive drugs and positive fluid balance are predictors of mortality in severe dengue infection in children admitted to PICU.

Assessment of airway reversibility in asthmatic children using forced oscillation technique - A single-center experience from North India.

BACKGROUND: Lung function testing is recommended for the management of asthma. Due to certain limitations of conventional spirometry in vulnerable patients, forced oscillation technique (FOT) has been studied with promising results. As there is a paucity of data from developing world, we planned to conduct this study in children using FOT. To assess airway reversibility after inhaled salbutamol in asymptomatic children with suspected asthma. SETTINGS: This study was conducted at pediatric asthma clinic of a tertiary care referral hospital in North India. DESIGN: This was a prospective interventional study over 1-year period. SUBJECTS AND METHODS: Asymptomatic children between 2 and 18 years of age, with history suggestive of asthma, were eligible for participation. Baseline and postbronchodilator pulmonary functions were assessed using FOT. Airway resistance and reactance were monitored at various frequencies. SPSS version 17 was used for statistical analysis. RESULTS: Among the 345 enrolled children, baseline mean ± standard deviation total airway resistance (R5), central airway resistance (R19), peripheral airway resistance (R5-R19), reactance (X5), and resonant frequency (Fres) were 6.85 ± 2.60, 5.23 ± 1.93, 1.6 ± 1.16, and - 2.54 ± 1.36 cmH2O/L/s and 17.28 ± 3.06 Hz. The median (interquartile range) percentage change after inhaled salbutamol was 19.9 (11.40, 29.12), 22.86 (6.88, 38.76), 14.08 (3.40, 22.62), 39.20 (8.20, 62.39), and 15.79 (8.33, 27.27) in respective parameters. All changes were statistically significant. The studied respiratory variables were in maximum negative correlation with height, followed by body mass index. CONCLUSIONS: FOT is a simple technique for monitoring lung functions in children during asthma management.

Chest sonography versus chest radiograph in children admitted to paediatric intensive care - A prospective study.

There is a paucity of studies on the correlation between chest radiograph and ultrasound (US) in children. Our objective was to study the correlation between bedside chest radiograph and ultrasound findings in 413 children with 1002 episodes of chest radiograph and US enrolled for a prospective, double-blinded observational study in a multidisciplinary paediatric intensive care unit. Weighted κ statistic for agreement was different for right and left lungs and varied from 50% for left pleural effusion to 98% for right pneumothorax. Pulmonary oedema, pneumothorax and pleural effusion were diagnosed by ultrasound alone in a significantly higher number of patients as compared to chest radiograph (P = 0.001). Chest ultrasound is therefore deemed more sensitive than chest radiograph in detection of pleural effusion, pulmonary oedema and pneumothorax.

IAP Guideline on Practicing Safely During COVID-19 Era: Clinics and Small Establishments.

JUSTIFICATION: The unprecedented COVID-19 pandemic has had a formidable impact on Indian health care. With no sight of its end as yet, various establishments including the smaller clinics and nursing homes are restarting full operations. Hence, there is the need for recommendations to allow safe practice ensuring the safety of both the heath care worker (HCW) and patients. PROCESS: Indian Academy of Pediatrics organized an online meeting of subject experts on 27 July, 2020. A committee was formed comprising of pediatricians, pediatric and neonatal intensivists, and hospital administrators. The committee held deliberations (online and via emails) and a final consensus was reached by November, 2020. OBJECTIVES: To develop recommendations to provide a safe and practical healthcare facility at clinics and small establishments during COVID times. RECOMMENDATIONS: The key recommendation to practise safely in this setting are enumerated. Firstly, organizing the out-patient department (OPD). Secondly, appropriate personal protective equipment (PPE) to provide protection to the individual. Thirdly, decontamination/disinfection of various common surfaces and equipment to prevent transmission of infection from fomites. Next, maintaining the heating ventilation and air conditioning (HVAC) to provide a stress-free, comfortable, and safe environment for patients and HCWs. Finally, steps to effectively manage COVID-19 exposures in a non-COVID-19 facility. All these measures will ensure safe practice during these unprecedent times in clinics and smaller establishments.

Electrocardiometry Fluid Responsiveness in Pediatric Septic Shock.

Hemodynamic monitoring and categorization of patients based on fluid responsiveness is the key to decisions prompting the use of fluids and vasoactive agents in septic shock. Distinguishing patients who are going to benefit from fluids from those who will not is of paramount importance as large amounts of fluids used conventionally based on surviving sepsis guidelines may be detrimental. Noninvasive monitoring techniques for the assessment of various cardiovascular parameters are increasingly accepted as the current medical practice. Electrical cardiometry (EC) is one such method for the determination of stroke volume, cardiac output (CO), and other hemodynamic parameters and is based on changes in electrical conductivity within the thorax. It has been validated against gold standard methods such as thermodilution [Malik V, Subramanian A, Chauhan S, et al. World J 2014;4(7):101-108] and is being used more often as a point-of-care noninvasive technique for hemodynamic monitoring. EC is Food and Drug Administration approved and validated for use in neonates, children, and adults. A meta-analysis in 2016, including 20 studies and 624 patients comparing the accuracy of CO measurement by using EC with other noninvasive technologies, demonstrated that EC was the device that offered the most correct measurements. The article in the current issue of IJCCM by Rao et al. (2020) has extended the use of EC to categorize pediatric patients with septic shock into vasodilated and vasoconstricted states based on systemic vascular resistance and correlate the categorization clinically. The authors also studied the changes in hemodynamic parameters after an isotonic fluid bolus of 20 mL/kg was administered. This is a pilot prospective observational study of 30 patients, which has given an insight into physiological rearrangements following fluid administration in patients with septic shock. How to cite this article: Gupta D, Dhingra. Electrocardiometry Fluid Responsiveness in Pediatric Septic Shock. Indian J Crit Care Med 2021;25(2):123-125.

Flexible Fiber-optic Bronchoscopy-directed Interventions in Children with Congenital Heart Diseases.

OBJECTIVE: In children, pulmonary and cardiac diseases are closely associated, and their integrated evaluation is important. Flexible fiber-optic bronchoscopy (FFB) can be used for both diagnostic and therapeutic purposes in pediatric cardiac intensive care units (PCICU). The objective of this study was to evaluate the utility of FFB in children with congenital heart disease (CHD). MATERIALS AND METHODS: A retrospective, descriptive study was conducted at a tertiary care center in pediatric patients who underwent FFB in PCICU over a period of 6 years (2012-2017). RESULTS: Total 71 bronchoscopies were done in 58 patients with CHD with median age and weight of 2.5 months and 3.4 kg, respectively. Total of 20 different cardiac lesions were present among patients who underwent FFB. While 38 (53.5%) and 30 (42.3%) procedures were performed in pre-op and postoperative patients, respectively, 3 intraoperative bronchoscopies were also performed. The main indications for FFB were persistent atelectasis (42/71), prolonged oxygen requirement (13/71), stridor (8/71), and suspected airway anomaly (6/71). Tracheobronchitis was the commonest bronchoscopy finding (51/71, 71.8%) followed by tracheobronchomalacia (27/71, 38.3%). Cause of stridor detected in 7/8 cases. Associated preoperative and postoperative respiratory complications were detected and necessary interventions were done. These included slide tracheoplasty (5/58), tracheostomy (5/58), antibiotic change based on bronchoalveolar lavage (BAL) cultures (11/71), and continued positive pressure ventilation (4/71). Nonconsequential complications were transient hypoxemia (10/71), bleeding (2/71), and transient bradycardia (1/71). CONCLUSION: Bedside FFB is a safe and a valuable diagnostic tool that also helps in guiding interventions in children with cardiac diseases. HOW TO CITE THIS ARTICLE: Sachdev A, Chhawchharia R, Gupta D, Gupta N, Joshi R, Agarwal N. Flexible Fiber-optic Bronchoscopy-directed Interventions in Children with Congenital Heart Diseases. Indian J Crit Care Med 2020;24(5):340-343.

Novel Coronavirus 2019 (2019-nCoV) Infection: Part I - Preparedness and Management in the Pediatric Intensive Care Unit in Resource-limited Settings.

First reported in China, the 2019 novel coronavirus has been spreading across the globe. Till 26 March, 2020, 416,686 cases have been diagnosed and 18,589 have died the world over. The coronavirus disease mainly starts with a respiratory illness and about 5-16% require intensive care management for acute respiratory distress syndrome (ARDS) and multi-organ dysfunction. Children account for about 1-2% of the total cases, and 6% of these fall under severe or critical category requiring pediatric intensive care unit (PICU) care. Diagnosis involves a combination of clinical and epidemiological features with laboratory confirmation. Preparedness strategies for managing this pandemic are the need of the hour, and involve setting up cohort ICUs with isolation rooms. Re-allocation of resources in managing this crisis involves careful planning, halting elective surgeries and training of healthcare workers. Strict adherence to infection control like personal protective equipment and disinfection is the key to contain the disease transmission. Although many therapies have been tried in various regions, there is a lack of strong evidence to recommend anti-virals or immunomodulatory drugs.

Novel Coronavirus 2019 (2019-nCoV) Infection: Part II - Respiratory Support in the Pediatric Intensive Care Unit in Resource-limited Settings.

The 2019-novel coronavirus predominantly affects the respiratory system with manifestations ranging from upper respiratory symptoms to full blown acute respiratory distress syndrome (ARDS). It is important to recognize the risk factors, categorize severity and provide early treatment. Use of high flow devices and non-invasive ventilation has been discouraged due to high chances of aerosol generation. Early intubation and mechanical ventilation areessential to prevent complications and worsening, especially in resource-limited settings with very few centers having expertise to manage critical cases. Hydrophobic viral filter in the ventilator circuit minimizes chances of transmission of virus. Strategies to manage ARDS in COVID-19 include low tidal volume ventilation with liberal sedation-analgesia. At the same time, prevention of transmission of the virus to healthcare workers is extremely important in the intensive care setting dealing with severe cases and requiring procedures generating aerosol. We, herein, provide guidance on non-invasive respiratory support, intubation and management of ARDS in a child with COVID-19.