Inclusion criteria: Infants with TGA/IVS younger than 3 months of age who underwent ASO in our hospital.

Exclusion criteria: We excluded patients who had been treated with PGE1 for more than 48 hours at other hospitals before admission, since the doses administered before transport were often poorly recorded and used empirically.

Bedside POCUS was performed by neonatologists with considerable experience in using a pulsed-wave Doppler (Mindray, Model 9T) equipped with a 3–7 MHz shallow-focus transducer. The PDA was imaged from the left parasternal position using a direct inferior or slightly superior position, and the minimum diameter was measured through frame-by-frame analysis. If the entire PDA could not be visualized through a standard parasternal approach, an alternative position was adopted, with the probe placed just below the right or left clavicle. The probe was rotated to align with the long axis of the aortic arch. Subsequently, the probe was turned downwards to visualize the PDA, the main pulmonary artery, and the aortic arch in the same section [20, 21]. The size of the PDA was assessed by measuring the minimum and maximum intraluminal diameters using two-dimensional echocardiography. The smallest measurement obtained at the pulmonary end of the ductus arteriosus, as determined by color-Doppler mapping, was defined as the ductal diameter [22]. An inner ductal diameter of less than 2 mm, as described above, was regarded as the first sign of ductal constriction [9, 23]. The PDA diameter was measured using echocardiography by two independent neonatologists trained in bedside ultrasound, with the average of three consecutive cardiac cycles recorded.

Baseline clinical characteristics, such as gender, gestational age, birth weight, and prenatal diagnosis, were documented. Medication records were reviewed to determine whether the patient had been transported on PGE1. We documented the total duration of PGE1 administration and any discontinuation or change in dose. PGE1 treatment success was defined as achieving a SpO₂ level within 70–85% before surgery. Due to the complexity and variability of the data, the patients were divided into two groups for analysis based on the dose of PGE1: Low-dose group (the PGE1 dose was less than 5 ng/kg$\cdot$min) and high-dose group (the PGE1 dose was higher than 5 ng/kg$\cdot$min or requiring the use of an impact dose of 20–100 ng/kg$\cdot$min). More detailed groupings were conducted based on the dosage used, from smallest to largest as follows: Group A, the PGE1 dose was rapidly reduced and stopped within 24 hours; Group B, the PGE1 dose was maintained at 1–5 ng/kg$\cdot$min without discontinuation; Group C, the PGE1 dose was 5–10 ng/kg$\cdot$min; Group D, with a dose exceeding 10 ng/kg$\cdot$min or requiring the use of an impact dose of 20–100 ng/kg$\cdot$min.

Seizures, respiratory depression, fever, and necrotizing enterocolitis (NEC) were recorded, and these conditions were carefully analyzed for the potential for adverse effects of PGE1. The need for enhanced respiratory support and/or caffeine for treating apnea was noted. When the PGE1 dose exceeded 10 ng/kg$\cdot$min, respiratory depression was particularly common. Caffeine was prescribed to decrease these risks [9, 11, 24, 25].

Descriptive statistics were employed to analyze the demographic and morbidity data. The normal distribution and equal variance were verified for continuous variables. The Shapiro–Wilk test was utilized to determine whether the numeric variables were normally distributed. Normally distributed data are presented as the mean $\pm$ standard deviation. Non-normally distributed data are presented as the median and the interquartile range. Differences among categorical variables were examined via Pearson’s chi-squared test or Fisher’s exact test. Differences in means between normally distributed continuous variables were assessed using the Student’s t-test or analysis of variance. We used logistic regression to estimate the association of POCUS with the dosage of PGE1. Variables with a value of p 0.1, as well as factors potentially associated with PGE1 administration, were included in the multivariate logistic regression analysis. The results are presented as odds ratios (OR) along with their corresponding 95% confidence intervals (CIs). All analyses were conducted using the IBM SPSS® Version 23.0 software (SPSS Inc., Chicago, IL, USA). Statistical significance was defined as p 0.05 for all analyses.

The rate of PGE1 use in the control group (93.3%) was significantly higher than in the POCUS group (71.1%; p 0.001). The initial initiation time of PGE1 use in the control group (prenatally diagnosed) was earlier than in the POCUS group (0.05 $\pm$ 0.01 d vs. 1.66 $\pm$ 3.72 d; p 0.001). The proportion of patients using low-dose PGE1 in the POCUS group was 40.6%, which was significantly higher than the 8.9% noted in the control group. The dose grouping ratios between the POCUS group and the control group were as follows: Group A (10.9% vs. 1.8%), Group B (29.7% vs. 7.1%), Group C (40.6% vs. 60.7%), and Group D (18.8% vs. 30.4%). All of the above were statistically significant differences (p 0.001; Table 2). There was no difference in the improvement of SpO₂ after using PGE1 between the two groups (p = 0.404; Table 2). The requirement for emergency surgery decreased in the POCUS group (p = 0.030; Table 1).

In infants receiving PGE1, there was no significant difference in the incidence of fever (p = 0.923) or respiratory depression (p = 0.697; Table 3) between the two groups. In Epoch 1, two cases in Group D and three cases in Group C developed respiratory depression, while five cases in Group D, three cases in Group C, one case in Group B, and one case in Group A developed a fever. In Epoch 2, one case in Group D, three cases in Group C, and two cases in Group B developed respiratory depression, while five cases in Group D, four cases in Group C, and two cases in Group B developed a fever (Table 3).

Consistent with contemporary methodological guidance (STROBE Statement 2007 [26]; Lee S 2017 [27]), our variable selection process explicitly balanced statistical criteria with domain knowledge derived from neonatal cardiac surgery studies (Kumar 2021 [28]). Variables with a value of p 0.1 from the univariate analysis, as well as those potentially associated with PGE1 administration, were included as independent variables in the multivariate logistic regression analysis using the Wald test. The results indicated that the use of POCUS significantly reduces the dosage of PGE1. Detailed findings are presented in Table 4.

Preoperative use of PGE1 in infants with TGA depends on the individual clinical indication. An intravenous (IV) infusion of PGE1 is recommended immediately after birth, until postnatal echocardiograms are completed and all forms of inter-circulatory mixing have been evaluated. PGE1 has been employed in diverse dosing regimens: a higher dose of up to 100 ng/kg$\cdot$min might be required when the ductus needs to be reopened [4, 5]. To maintain ductal patency, standard doses range from 10 to 50 ng/kg$\cdot$min. Patients can be tapered off starting 2–4 hours after initiation, provided that SpO₂ levels and tissue perfusion remain acceptable [4, 5, 6, 7, 8].

Adverse drug events of PGE1 included apnea, tachypnea, bradycardia, tachycardia, hypotension, hypokalemia, hyperkalemia, hypocalcemia, fever, tremors, bleeding, edema, neurologic side effects, necrotizing enterocolitis, and cortical hyperostosis [8, 9]. Since our study was retrospective, some clinical symptoms were not fully recorded. The adverse effects of PGE1 focused mainly on respiratory depression and fever.

At an initial dose of 25 to 50 ng/kg$\cdot$min, apnea occurred in 42%, while intubation due to respiratory depression occurred in 14% of infants as reported by Tálosi et al. [19]. Other studies have explored lower doses of PGE1 and reported a lower incidence of respiratory depression [30, 34]. There is evidence indicating that respiratory depression induced by PGE1 is dose-dependent [12, 35], although one study contradicts this finding [29]. However, we could not confirm that a lower dose of PGE1 could reduce the risk of respiratory depression (9.4% vs. 8.9%; p = 0.697). Our cohort reported an overall rate of clinically relevant respiratory depression of 9.2%, and all these patients required mechanical ventilation due to respiratory depression. The accurate assessment of the risk of respiratory depression had been hindered since nearly half of the children required non-invasive or mechanical ventilation as a result of their condition either before or after PGE1 usage. When administering PGE1 at a dosage exceeding 10 ng/kg$\cdot$min, it was advisable to use caffeine to prevent apnea. Moreover, we found that the children in the control group of this study were more often transferred from other hospitals and were older at the time of diagnosis. The initiating use of PGE1 might indicate a stronger tolerance to PGE1. This suggests that there are many confounding factors for the dosage of PGE1, and that studies with larger sample sizes are needed. We found that the overall rate of clinically relevant fever was 17.5% in our study. There was no significant difference between the POCUS group and the control group (17.2% vs. 17.9%; p = 0.095).

Our data found that even low-dose (less than 5 ng/kg$\cdot$min) PGE1 was at risk of respiratory depression, which may be affected by preterm birth, low birth weight, the early postnatal period, and cardiac insufficiency. This is consistent with other studies [16, 30]. Therefore, regardless of whether the side effects of PGE1 are dose-dependent, a lower dose of PGE1 does not appear to increase the risk of respiratory depression or fever.

POCUS is a non-invasive, low-risk imaging modality that can be used to diagnose and help guide the management of critically ill children in the cardiac intensive care unit. POCUS can be performed by an intensivist at the bedside of patients with real-time interpretation, leading to rapid clinical decision-making and the potential to improve patient outcomes [36]. Recent studies support the use of POCUS for accurately assessing left ventricular systolic function, diagnosing pericardial effusion, pulmonary embolism, identifying pulmonary edema and pneumonia, as well as consensus statements on the use of cardiac and lung POCUS in clinical practice [37, 38]. The Society of Point of Care Ultrasound (SPOCUS) formed a working group in 2022 to establish a set of recommended best practices for POCUS, applicable to clinicians regardless of their training, specialty, resource setting, or scope of practice [39]. However, achieving real-time bedside monitoring of PDA dimensions to guide pharmacological interventions and clinical decision-making remains a significant challenge in pediatric patients with cyanotic congenital heart disease. The training program for senior residents at our institution spans a duration of 1 to 3 years. Will such training face significant challenges? A study described the national state of POCUS training in residency programs and evaluated the implementation of the core POCUS curriculum in Canada [40]. POCUS leaders believe their residents are proficient in the core POCUS applications by the end of training, except for advanced cardiac and thoracic ultrasound. It is believed that senior doctors from high-level centers can meet the training requirements and widely apply POCUS to provide better clinical strategies for patients.