Fluid resuscitation in children with severe infection and septic shock: a systematic review and meta-analysis.

This study aimed to evaluate the current evidence on various aspects of fluid therapy such as type, volume, and timing of fluid bolus administration in children with septic shock. Systematic review and meta-analysis of clinical trials including children less than 18 years of age admitted to the pediatric emergency and intensive care unit with severe infection and shock requiring fluid resuscitation. The intervention included balanced crystalloids (BC) vs normal saline (NS), colloids vs NS, restricted vs liberal fluid bolus, and slow vs fast fluid bolus. The primary outcome was mortality rate. Of the 219 citations retrieved, 12 trials (3526 children with severe infection with or without malaria and shock) were included. The pooled results found no significant difference in the mortality rate between groups comparing balanced crystalloids (BC) vs normal saline (NS), colloids vs NS, restricted vs liberal fluid bolus, and slow vs fast fluid bolus. The risk of acute kidney injury (AKI) was significantly less in the BC group compared to the NS group. The certainty of evidence for mortality was of "moderate certainty" in the BC vs NS group, and was of "very low certainty" for the other two groups. CONCLUSIONS: The current meta-analysis found no significant difference in the mortality rate between the types of resuscitation fluid, and their speed or volume of administration. However, a significantly decreased risk of AKI was found in the BC group. More evidence is needed regarding the speed and volume of administration of fluid boluses in critically ill children.Prospero registration: CRD42020209066. WHAT IS KNOWN: • Balanced crystalloids (BC) may be better than normal saline (NS) for fluid resuscitation in critically ill children. WHAT IS NEW: • BC are better than NS for fluid resuscitation in critically ill children as they decrease AKI and hyperchloremia.

Effect of Imatinib Mesylate on Growth in Pediatric Chronic Myeloid Leukemia: A Systematic Review and Meta-analysis.

The outcomes of pediatric chronic myeloid leukemia (CML) have improved with the use of imatinib mesylate (IM). Multiple reports of growth deceleration with IM have raised concerns, necessitating careful monitoring and evaluation in children with CML. We systematically searched the databases of PubMed, EMBASE, Scopus, CENTRAL, and conferences-abstracts, reporting the effect of IM on growth among children with CML, and published in the English language from inception till March 2022. For observational studies, the modified Newcastle Ottawa Scale was used to assess the risk of bias. Pooled estimates were derived using a random-effects meta-analysis, and heterogeneity was assessed using Cochrane Q statistic test of heterogeneity and I2 statistic. Of the 757 studies identified through electronic search, 15 (n=265) were included in the final analysis. Six studies (n=178) were included in the meta-analysis of the primary outcome. There was a significant deleterious effect of IM on height-standardized mean difference (SMD): -0.52 (95% CI: -0.76; -0.28) ( I2 =13%). The adverse effect of IM on height was significant among studies with a follow-up period <3 years [SMD: -0.66 (95% CI: -0.93, -0.40), I2 =0%, P =0.59] but not in studies with follow-up period ≥3 years [SMD: -0.26 (95% CI: -0.63, 0.11), I2 =0, P =0.44], indicating that the effect of IM on height is a short-term effect. The effect of IM on height was not dependent upon pubertal status at the initiation of therapy. Prospective studies with adequate sample size are required to confirm the findings of the effect of IM on height in children with CML.

Assessment of Cardiorespiratory Fitness in 8-to-15-Year-Old Children with Overweight/Obesity by Three-Minute Step Test: Association with Degree of Obesity, Blood Pressure, and Insulin Resistance.

OBJECTIVE: To assess cardiorespiratory fitness in children and adolescents with overweight/obesity using the Kasch pulse recovery (KPR) test, and its correlation with severity of obesity, insulin resistance, and blood pressure (BP). METHODS: This is a retrospective analysis of baseline data from a study evaluating the efficacy of yoga for reduction of body mass index (BMI) in children aged 8-15 y with overweight/obesity. KPR three-minute step test was done. Children were classified into cardiorespiratory fitness categories based on the post-KPR heart rate (HR); the maximal oxygen consumption (VO2 max) was calculated, and the correlation analysis was done. RESULTS: One hundred fifty-five children with mean age of 11.6 ± 1.8 y and mean BMI of 26.2 ± 4.1 kg/m2 were included. Mean post-KPR-HR and calculated VO2 max were 119 ± 14 per minute and 48.7 ± 5.6 mL/kg/min, respectively. In children < 13 y, cardiorespiratory fitness was excellent or very good in 28%, good or sufficient in 58%, and poor or very poor in 14%. BMI, waist circumference (WC), resting HR, systolic BP, and homeostatic model of insulin resistance (HOMA-IR) were higher among those with poor/very poor fitness, with WC z score being statistically significant (p = 0.015). Post-KPR-HR showed positive correlation with BMI z score (r = 0.16, p = 0.044), WC z score (r = 0.21, p = 0.011), and HOMA-IR (r = 0.22, p = 0.012). CONCLUSION: In children with overweight/obesity, 14% had poor cardiorespiratory fitness. Post-KPR-HR and calculated VO2 max had good correlation with measures of obesity and HOMA-IR. Further studies evaluating cardiorespiratory fitness and normative data of VO2 max for Indian children are warranted.

Utility of Inferior Vena Cava Distensibility and Respiratory Variation in Peak Aortic Blood Flow Velocity to Predict Fluid Responsiveness in Children with Shock.

OBJECTIVES: To evaluate the sensitivity and specificity of inferior vena cava (IVC) distensibility index (∆IVC) and respiratory variation in peak aortic blood flow velocity (∆Vpeak) to predict fluid responsiveness in ventilated children with shock and to find out the best cut-off values for predicting fluid responsiveness. METHODS: In this prospective observational study, conducted in a pediatric ICU from January 2019 through May 2020, consecutive children aged 2 mo to 17 y with shock requiring fluid bolus were included. ∆IVC and ∆Vpeak were measured before and immediately after 10 ml/kg fluid bolus administration. ∆IVC and ∆Vpeak were compared between responders and non-responders, defined by a change in stroke volume index (SVI) of ≥10%. RESULTS: Thirty-seven ventilated children [26 (70.4%) boys] with median age of 60 (36, 108) mo were included. The median (IQR) ∆IVC was 21.7% (14.3, 30.9) and the median (IQR) ΔVpeak was 11.3% (7.2, 15.2). Twenty-three (62%) children were fluid responsive. The median (IQR) ∆IVC was higher in responders compared to non-responders [26% (16.9, 36.5) vs. 17.2% (8.4, 21.9); p = 0.018] and mean (SD) ΔVpeak was higher in responders [13.9% (6.1) vs. 8.4% (3.9), p = 0.004]. The prediction of fluid responsiveness with ΔIVC [ROC curve area 0.73 (0.56-0.9), p = 0.01] and ΔVpeak [ROC curve area 0.78 (0.63-0.94), p = 0.002] was similar. The best cut-off of ∆IVC to predict fluid responsiveness was 23% (sensitivity, 60.8%; specificity, 85.7%) and ΔVpeak was 11.3% (sensitivity, 74%; specificity, 86%). CONCLUSIONS: In this study, authors found that ∆IVC and ΔVpeak were good predictors of fluid responsiveness in ventilated children with shock.

A Randomized Controlled Trial of Norepinephrine Plus Dobutamine Versus Epinephrine As First-Line Vasoactive Agents in Children With Fluid Refractory Cold Septic Shock.

Our objective was to compare norepinephrine plus dobutamine versus epinephrine as the first-line agent in children with fluid refractory cold septic shock. DESIGN: Open-label randomized controlled study. SETTING: A single-center PICU from North India. PATIENTS: Children 2 months to less than 18 years old with fluid refractory cold septic shock. INTERVENTIONS: In the intervention group, norepinephrine and dobutamine were started and in the control group, epinephrine was started as the first-line vasoactive agent. The primary outcome was the proportion attaining shock resolution (attaining all the therapeutic endpoints) at 1 hour of therapy. MEASUREMENTS AND MAIN RESULTS: We enrolled 67 children: 34 in the norepinephrine plus dobutamine group (intervention) and 33 in the epinephrine group (control). There was no difference in shock resolution at 1 hour (17.6% vs 9%; risk ratio [RR], 2.0; 95% CI, 0.54-7.35; p = 0.25), 6 hours (76.4% vs 54.5%; RR, 1.69; 95% CI, 0.92-3.13; p = 0.06), and 24 hours between the intervention and control groups, respectively. Children in the norepinephrine plus dobutamine group attained shock resolution earlier (measured from starting of vasoactive agents to attaining all the therapeutic endpoints) (hazard ratio, 1.84 [1.1-3.08]). The difference in 28-day mortality was not significant (23.5% vs 39.3% in the intervention and control groups, respectively [RR, 0.59; 95% CI, 0.28-1.25]). CONCLUSIONS: In children with fluid refractory cold septic shock, with use of norepinephrine plus dobutamine as first-line agents, the difference in the proportion of children attaining shock resolution at 1 hour between the groups was inconclusive. However, the time to shock resolution was earlier in the norepinephrine plus dobutamine group. Also, fewer children in the intervention group were refractory to treatment. Further studies powered to detect (or exclude) an important difference would be required to test this intervention.

Outcomes of Children with Unoperated Congenital Heart Disease Admitted to PICU-A Single-Center Experience.

OBJECTIVES: To evaluate the outcomes of children with congenital heart disease (CHD) awaiting surgery admitted to a pediatric intensive care unit (PICU) with acute illness. METHODS: In this retrospective study from a single center, the outcomes of children up to 18 y of age with unoperated CHD admitted to PICU with acute illness and factors affecting the outcomes, were evaluated. RESULTS: Fifty-eight (41 boys) children were included. Median age was 3.2 (1.5, 6) mo. Thirty-six (62%) children had acyanotic CHD (ACHD), and 22 (38%) had cyanotic CHD (CCHD). Most common ACHD was ventricular septal defect (n = 14; 38.8%) and CCHD was double-outlet right ventricle (n = 6; 27.2%). Twenty-four (41%) children underwent surgery - 10 (41.6%) palliative procedure and 14 (58.3%) corrective procedure. Hospital mortality was 50%. Of the operated children, 37.5% died and of the nonoperated children, 58.8% died. Type of the heart disease and surgical intervention was not associated with mortality (p = 0.27 and 0.11). Requirement of vasoactive agents was associated with increased mortality (p = 0.02). In children with ACHD, factors associated with mortality were lower score for weight for age (p = 0.03) and weight for length (p = 0.04), lower admission pH (p = 0.02), hemodynamic instability at admission (p = 0.002), and requirement of vasoactive agents (p = 0.04). CONCLUSION: Children with unoperated CHD with acute illness have high morbidity and mortality. Early diagnosis and surgical interventions in children with CHD are warranted. TRIAL REGISTRATION: Trial Registration No. IECPG-571/21.10.2020.

Case Report: Extensive Gangrene: A Rare Presentation of Multisystem Inflammatory Syndrome in Children.

A wide spectrum of cutaneous manifestations are reported in multisystem inflammatory syndrome in children (MIS-C). However, gangrenous changes are less frequently reported. A 3-year old boy, with a known case of unoperated tetralogy of Fallot, presented with a short history of fever, rash, and melena. The rash was black and diffuse, with a rapid progression. The patient was stable hemodynamically at admission, with pallor, grade II clubbing, edema, and oral ulcers. Inflammatory markers were raised. He developed gangrenous changes over the ears and acral areas. He had very high levels of antibodies to severe acute respiratory syndrome coronavirus2 (SARS-CoV-2) infection and was diagnosed as having MIS-C. Skin biopsy revealed near total epidermal necrosis with dermal vascular thrombi and negative immunofluorescence. Skin biopsy was positive for IgG antibodies to SARS-CoV-2. He was treated with antibiotics, immunomodulation with steroids, intravenous immunoglobulin, and plasmapheresis. He had features of both micro- and macroangiopathy. Gradually the child improved, with residual deformity.

Allergic Bronchopulmonary Aspergillosis in Children Presenting as Lung Masses.

Allergic bronchopulmonary aspergillosis (ABPA) is an IgE-mediated hypersensitivity reaction predominantly occurring in patients of asthma and cystic fibrosis. The typical radiological findings in ABPA include central bronchiectasis and fleeting opacities. In this retrospective study, the aim was to describe cases of ABPA in children who had a mass-like lesion in the lung. There were 5 cases of ABPA in children, who presented as mass-like lesions that responded very well to treatment for ABPA. All cases, except 1, had asthma as the underlying disease. There was a delay in the diagnosis of ABPA in all 5 cases. There had been unnecessary invasive investigations in some of these cases before the diagnosis of ABPA was made. To conclude, children with ABPA may present with a mass-like lesion in the lung and high index of suspicion is required to diagnose ABPA timely to prevent its consequences.