Theofili Kousi

Background: Midazolam is widely used as a pediatric premedication, but evidence from direct comparisons of oral and sublingual administration in children with congenital heart disease remains limited, particularly that from pharmacokinetic and physiologic data analyzed together. Methods: We conducted a single-center prospective randomized study comparing oral midazolam 0.5 mg/kg with sublingual midazolam 0.3 mg/kg in children undergoing cardiac surgery or catheterization procedures under general anesthesia. Plasma midazolam and 1-hydroxymidazolam concentrations were measured approximately 30 min after administration. Log-transformed concentrations were compared using regression/ANCOVA models adjusted for dose and age. Changes in mean arterial pressure (MAP), heart rate (HR), and oxygen saturation (SpO₂) were analyzed from baseline to 15 and 30 min. Behavioral outcomes included the sedation score, separation from parents, and mask acceptance. Results: Sixty-eight children were randomized; 65 had evaluable pharmacokinetic samples and formed the complete-case pharmacokinetic cohort. Adjusted plasma midazolam concentrations did not differ significantly between the groups, with an adjusted geometric mean ratio for sublingual versus oral administration of 0.98 (95% CI 0.53–1.79; unadjusted p = 0.940; Holm-adjusted p = 1.000). The corresponding ratio for 1-hydroxymidazolam was 1.37 (95% CI 0.55–3.41; unadjusted p = 0.494; Holm-adjusted p = 1.000). HR and SpO₂ changes were non-significant between the groups. At 30 min, sublingual administration was associated with a lower adjusted change in MAP compared with oral administration (adjusted difference −12.08 mmHg, 95% CI −19.74 to −4.42; unadjusted p = 0.002, Holm-adjusted p = 0.012). Behavioral outcomes did not differ significantly between the groups. Conclusions: In this prospective randomized pediatric cardiac cohort, oral midazolam 0.5 mg/kg and sublingual midazolam 0.3 mg/kg produced comparable plasma concentrations and similar behavioral outcomes. Sublingual administration was not associated with worse HR or SpO₂ responses, although an isolated lower MAP change at 30 min warrants confirmation in larger studies. Sublingual midazolam may represent a feasible lower-dose alternative for premedication in this population.

Background: Midazolam is widely used as pediatric premedication, but evidence directly comparing oral and sublingual administration in children with congenital heart disease remains limited, particularly when pharmacokinetic and physiologic data are analyzed together. Methods: We conducted a single-center prospective randomized study comparing oral midazolam 0.5 mg/kg with sublingual midazolam 0.3 mg/kg in children undergoing cardiac surgery or catheterization procedures under general anesthesia. Plasma midazolam and 1-hydroxymidazolam concentrations were measured approximately 30 minutes after administration. Log-transformed concentrations were compared using regression/ANCOVA models adjusted for dose and age. Changes in mean arterial pressure (MAP), heart rate (HR), and oxygen saturation (SpO2) were analyzed from baseline to 15 and 30 minutes. Behavioral outcomes included sedation score, separation from parents, and mask acceptance. Results: Sixty-eight children were randomized; 65 had evaluable pharmacokinetic samples and formed the complete-case pharmacokinetic cohort. Adjusted plasma midazolam concentrations did not differ significantly between groups, with an adjusted geometric mean ratio for sublingual versus oral administration of 0.98 (95% CI 0.53-1.79; p=0.940). The corresponding ratio for 1-hydroxymidazolam was 1.37 (95% CI 0.55-3.41; p=0.494). HR and SpO2 changes were similar between groups. At 30 minutes, sublingual administration was associated with a lower adjusted change in MAP compared with oral administration (adjusted difference -12.08 mmHg, 95% CI -19.74 to -4.42; p=0.002). Behavioral outcomes were comparable between groups. Conclusions: In this prospective randomized pediatric cardiac cohort, oral midazolam 0.5 mg/kg and sublingual midazolam 0.3 mg/kg produced comparable plasma concentrations and similar behavioral outcomes. Sublingual administration was not associated with worse HR or SpO2 responses, although an isolated lower MAP change at 30 minutes warrants confirmation in larger studies. Sublingual midazolam may represent a feasible lower-dose alternative for premedication in this population.

Acute Kidney Injury (AKI) commonly complicates cardiac surgery in children with congenital heart disease (CHD). In this study we assessed incidence, risk factors, and outcomes of postoperative AKI, while testing the hypothesis that, depending on the underlying diagnosis, there would be significant differences in AKI incidence among different diagnostic groups. We conducted an observational cohort study of children with CHD undergoing cardiac surgery in a single tertiary center between January 2019 and August 2021 (n = 362). Kidney Disease Improving Global Outcome (KDIGO) criteria were used to determine the incidence of postoperative AKI. Diagnosis was incorporated into multivariate models using an anatomic-based CHD classification system. Overall survival was estimated using Kaplan–Meier curves. Log-rank test and adjusted Cox proportional hazard modelling were used to test for differences in survival distributions and determine AKI effect on survival function, respectively. AKI occurred in 70 (19.3%), with 21.4% in-hospital mortality for AKI group. Younger age, lower weight, longer cardiopulmonary bypass time, preoperative mechanical ventilation and diagnostic category were associated with postoperative AKI. Resolution rate was 92.7% prior to hospital discharge for survivors. AKI was associated with longer duration of mechanical ventilation, ICU and hospital length of stay. AKI patients had significantly higher probability of all-cause mortality postoperatively when compared to the non-AKI group (log-rank test, p < 0.001). Adjusted hazard ratio for AKI versus non-AKI group was 11.08 (95% CI 2.45–50.01; p = 0.002). Diagnostic category was associated with cardiac surgery-related AKI in children with CHD, a finding supporting the development of lesion specific models for risk stratification. Postoperative AKI had detrimental impact on clinical outcomes and was associated with decreased survival to hospital discharge.

Right superior vena cava draining into the left atrium is an extremely rare anomaly of systemic venous return. It can be isolated or it can be associated with other congenital heart defects, thus clinical presentation may vary. A case of a 9‐year‐old asymptomatic patient with sinus venous defect and bilateral superior vena cava with the right‐sided draining into the left atrium is described.

Key Clinical Message: Although many variations regarding lobar or segmental bronchial subdivisions have been described, abnormal bronchi originating from the trachea or main bronchi are relatively rare. These abnormalities can remain undetectable as they usually do not present with symptoms; however, they may pose major obstacles during surgery especially when accompanied by bronchial wall abnormalities.