A Study to Compare Ultrasound-guided and Clinically Guided Fluid Management in Children with Septic Shock.

Background: To evaluate the role of ultrasound during initial fluid resuscitation along with clinical guidance in reducing the incidence of fluid overload on day 3 in children with septic shock. Materials and methods: It was a prospective, parallel limb open-labeled randomized controlled superiority trial done in the PICU of a government-aided tertiary care hospital in Eastern India. Patient enrolment took place between June 2021 and March 2022. Fifty-six children aged between 1 month and 12 years, with proven or suspected septic shock, were randomized to receive either ultrasound-guided or clinically guided fluid boluses (1:1 ratio) and subsequently followed up for various outcomes. The primary outcome was frequency of fluid overload on day 3 of admission. The treatment group received ultrasound-guided fluid boluses along with the clinical guidance and the control group received the same but without ultrasound guidance upto 60 mL/kg of fluid boluses. Results: The frequency of fluid overload on day 3 of admission was significantly lower in the ultrasound group (25% vs 62%, p = 0.012) as was the median (IQR) cumulative fluid balance percentage on day 3 [6.5 (3.3-10.3) vs 11.3 (5.4-17.5), p = 0.02]. The amount of fluid bolus administered was also significantly lower by ultrasound [median 40 (30-50) vs 50 (40-80) mL/kg, p = 0.003]. Resuscitation time was shorter in the ultrasound group (13.4 ± 5.6 vs 20.5 ± 8 h, p = 0.002). Conclusion: Ultrasound-guided fluid boluses were found to be significantly better than clinically guided therapy, in preventing fluid overload and its associated complications in children with septic shock. These factors make ultrasound a potentially useful tool for resuscitation of children with septic shock in the PICU. How to cite this article: Kaiser RS, Sarkar M, Raut SK, Mahapatra MK, Uz Zaman MA, Roy O, et al. A Study to Compare Ultrasound-guided and Clinically Guided Fluid Management in Children with Septic Shock. Indian J Crit Care Med 2023;27(2):139-146.

Role of lung ultrasound patterns in monitoring coronavirus disease 2019 pneumonia and acute respiratory distress syndrome in children.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, lung ultrasonography (US) has been gaining importance in pediatric intensive care and emergency settings for the screening, diagnosis, and monitoring of pulmonary pathology. PURPOSE: To describe the pattern of lung US changes in patients with COVID-19 pneumonia and its potential role in monitoring ventilated patients. METHODS: This prospective observational study included children aged 1 month to 12 years with a confirmed diagnosis of COVID-19. Lung US was performed using a high-frequency linear probe (5-12 MHz) in all children with moderate/severe respiratory symptoms within 24 hours of admission and then daily until the patient required oxygen therapy. Lung involvement severity was assessed using lung US scores, while lung aeration improvement or deterioration was measured using lung ultrasound reaeration scores (LUSReS). RESULTS: Of 85 children with moderate to severe disease, 54 with pulmonary disease were included. Of them, 50 (92.5%) had an interstitial pattern, followed by pleural line abnormalities in 44 (81.5%), reduced or absent lung sliding in 31 (57.4%), and consolidation in 28 (51.8%). A significantly higher lung US score (median, 18; interquartile range [IQR], 11-22) was observed in ventilated versus nonventilated patients (median, 9; IQR, 6-11). LUSReS improvement after positive end-expiratory pressure titration was positively correlated with improved dynamic lung compliance and oxygenation indices and negatively correlated with the requirement for driving pressure. Successful weaning could be predicted with 100% specificity if loss of LUSReS ≤ 5. CONCLUSION: Interstitial syndrome, fragmented pleural line, and subpleural microconsolidation were the most prevalent lung US findings in children with COVID-19 pneumonia. Thus, lung US may have the ability to monitor changes in lung aeration caused by mechanical ventilation and predict its successful weaning in children with COVID-19.

Clinical Characteristics of Children With SARS-CoV-2 Infection During the Third Wave of the Pandemic: Single Center Experience.

OBJECTIVE: To evaluate pulmonary functions in children with transfusion-dependent thalassemia, and its reversal (lung dysfunction) using intensive intravenous chelation with desferrioxamine (DFO) (4 weeks). METHODS: This descriptive study enrolled 77 children with transfusion-dependent thalassemia. Pulmonary function test (PFT) and iron load (serum ferritin (SF) and T2* MRI of heart and liver) were done. PFT included spirometry, total lung capacity (TLC) by helium dilution test and diffusion capacity by carbon monoxide (DLCO). Follow-up PFT was available for 13 children with moderate to severe lung dysfunction given intravenous DFO. RESULTS: 50 (68.8%) patients had lung dysfunction, most commonly diffusional impairment (48; 96%), and reduced TLC (11; 22%); and none had obstructive pattern. 9 (81.8%) patients with restrictive defect had moderate to severely deranged DLCO. PFT and T2* MRI values were inversely correlated with serum ferritin. Among 13 patients receiving intensive chelation for 4 weeks, significant improvement was noticed in forced expiratory volume in one minute/ forced vital capacity ratio (DFEV1/FVC) (P=0.009), DDLCO (P=0.006) and DSF (P=0.01). CONCLUSIONS: Pulmonary dysfunction is common in children with multi-transfused thalassemia, and routine screening by PFT needs to be part of the management guidelines.

Tracheostomy before 14 Days: Is It Associated with Better Outcomes in Pediatric Patients on Prolonged Mechanical Ventilation?

INTRODUCTION: With the advancement of pediatric critical care services across India, many children require prolonged mechanical ventilation (MV), and tracheostomy is recommended to them. However, many pediatric intensivists have concerns regarding the safety, feasibility, and outcome of tracheostomy.We aimed to analyze clinical characteristics, indication, duration, and outcome of tracheostomized children with respect to timing of tracheostomy. MATERIALS AND METHODS: We conducted a retrospective study from the hospital clinical database of consecutive patients below 12 years who had undergone tracheostomy after admission into the pediatric intensive care unit (PICU) for prolonged ventilation (≥96 hours) from January 2015 to December 2019. The study was approved by the Institutional Ethics Committee. Patients were divided into two groups: tracheostomies done within 14 days of MV (early tracheostomy) and patients with tracheostomies performed after 14 days (late tracheostomy). Patients' age, sex, indications, complications, decannulation rate, length of MV, PICU, and hospital stay were analyzed. RESULTS: Of the 1,425 patients on invasive MV, 87 (6.1%) patients required tracheostomy after a mean 13.37 days of MV. The most common indication was encephalopathy 32 (36.7%) followed by acute respiratory distress syndrome 20 (22.9%). Factors like higher pediatric logistic organ dysfunction score, vasoactive inotrop score, incidence of pretracheostomy ventilator-associated pneumonia, and difficulty in obtaining parental consent were associated with late tracheostomy. The early tracheostomy group had a higher decannulation rate (odds ratio, 5.17; p, 0.01) and weaning rate (odds ratio, 5.94; p, 0.032). The late tracheostomy group needed a longer duration of MV, PICU, and hospital stay. Complications of tracheostomy were less in the early tracheostomy patients (odds ratio, 2.95; p, 0.03). CONCLUSION: Early tracheostomy was associated with lower complications, higher successful weaning rates, and less utilization of intensive care facilities in patients receiving prolonged MV. CLINICAL SIGNIFICANCE: In the context of scarcity of data on the timing of tracheostomy in children with prolonged ventilation (≥96 hours) the study shows that early (<14 days) tracheostomy is associated with a better outcome. HOW TO CITE THIS ARTICLE: Sarkar M, Roychowdhoury S, Bhakta S, Raut S, Nandi M. Tracheostomy before 14 Days: Is It Associated with Better Outcomes in Pediatric Patients on Prolonged Mechanical Ventilation? Indian J Crit Care Med 2021;25(4):435-440.

Incomplete Kawasaki Disease as Presentation of COVID-19 Infection in an Infant: A Case Report.

BACKGROUND: Recently a severe form of COVID-19 infection has been described in a cluster of children presenting as multisystem inflammatory condition. One of the important spectrum of this condition is incomplete Kawasaki disease (KD). CASE REPORT: A 5-month-old male child presented with high-spiking fever for 5 days with skin rash, bilateral non-purulent conjunctivitis and irritability. His C-reactive protein was markedly elevated (215.4 mg/l). Echocardiography revealed dilated left main coronary artery (3.0 mm, Z score +4.30) and left anterior descending artery (2.37 mm, Z score +3.76). Concomitantly Reverse Transcription- Polymerase Chain Reaction for COVID-19 was positive on fifth day sample. He was diagnosed as incomplete KD with COVID-19 infection and treated with intravenous immunoglobulin (IVIG) (2 g/kg), oral aspirin and azithromycin. Patient improved after 48 h and was discharged on oral aspirin. CONCLUSION: Incomplete KD may co-exist with COVID-19 infection in infant. Early institution of IVIG may lead to better outcome.

Viral mononeurities causing partial oculomotor nerve palsy in an 8 month old child.

BACKGROUND: Palsy of the oculomotor nerve is rarely seen in children, and comprehensive guidelines for management and outcome are difficult to find. CASE: Here we describe a 8 month old boy with left sided ptosis and infero-leteral deviation of left eye and normally reacting pupil and CSF antimeasles antibody titre negative. OUTCOME: The ptosis improved within 3 weeks with no residual neurodeficit. MESSAGE: Viral mononeuritis leading to partial 3rd nerve palsy is a rare entity in children till date.

Developing oral drug delivery systems using formulation by design: vital precepts, retrospect and prospects.

INTRODUCTION: Over the past few decades, the domain of drug formulations has metamorphosed from the conventional tablets and capsules to advanced and intricate drug delivery systems (DDS), both temporal and spatial. Formulation development of the oral DDS, accordingly, cannot be adequately accomplished using the traditional 'trial and error' approaches of one variable at a time. This calls for the adoption of rational, systematized, efficient and cost-efficient strategies using 'design of experiments (DoE)'. The recent regulatory guidelines issued by the key federal agencies to practice 'quality by design (QbD)' paradigms have coerced researchers in industrial milieu, in particular, to use experimental designs during drug product development. AREAS COVERED: This review article describes these principles of DoE and QbD as applicable to drug delivery development using a more apt expression, that is, 'formulation by design (FbD)'. The manuscript describes the overall FbD methodology along with a summary of various experimental designs and their application in formulating oral DDS. The article also acts as a ready reckoner for FbD terminologies and methodologies. Select literature and an extensive FbD case study have been included to provide the reader with a comprehensive portrayal of the FbD precept. EXPERT OPINION: FbD is a holistic concept of formulation development aiming to design more efficacious, safe, economical and patient-compliant DDS. With the recent regulatory quality initiatives, implementation of FbD has now become an integral part of drug industry and academic research.