7 Efficacy of Pharmacologic Therapy for Patent Ductus Arteriosus Closure in Preterm Newborns According to Their Gestational Age-Specific Z-Score for Birth Weight

Primary Subject area Neonatal-Perinatal Medicine Background Preterm infants who are also intrauterine growth restricted (IUGR) experience more frequent and earlier hemodynamic consequences of patent ductus arteriosus (PDA). This may be related to altered levels of prostaglandins or altered number or sensitivity of their receptors in IGUR infants. Few studies have examined the efficacy of pharmacologic therapy (non-steroidal anti-inflammatory drugs [NSAIDs]: indomethacin, ibuprofen, or acetaminophen) for PDA closure among preterm infants based on their degree of IUGR with differing results. Objectives Primary: To determine if the degree of IUGR [defined by birth weight (BW) z-score] affects the efficacy of pharmacologic PDA closure and rate of surgical PDA ligation in preterm infants. Secondary: To compare the side effects of NSAIDs and neonatal outcomes based on the severity of IUGR. Design/Methods This retrospective cohort study included infants of < 30 weeks’ GA, admitted to a tertiary neonatal intensive care unit (NICU) between 2010 and 2018, with hemodynamically significant PDA and treated with NSAIDs. Infants with major congenital anomalies, those who received prophylactic Indomethacin and those who died in the first 48 hours were excluded. Birth weight (BW) z-scores were calculated using Olsen nomograms and classified into 3 categories: z-score > −0.5 (normal), z-score −0.5 to −2.0 (mild to moderate growth restriction), z-score <−2 (severe IUGR). We compared responses to NSAID treatment and PDA ligation. Multivariate logistic regression analysis was done to examine the association of BW z-score and response to pharmacological therapy and subsequent surgical PDA ligation. Results Of the 1511 eligible infants, 769 (51%) had a diagnosis of PDA. Of 517 included infants, 323 (62.5%) had BW z-score >− 0.5, while 154 (29.8%) had z-scores − 0.5 to −2.0 and 40 (7.7%) had z-score < −2. Table 1 shows their demographic characteristics. Efficacy of first course of NSAIDs was not different among these birth weight groups (Table 2). There was no difference in the side effects and neonatal morbidities amongst the three groups (Table 2). Multivariate logistic regression analysis after controlling for GA, gender, antenatal steroids, C-section, and SNAP II showed that the odds of PDA ligation was significantly higher among infants with BW z-score < −2 (aOR 2.68, 95% CI 1.13- 6.36) but not among infants with z-score −0.5 to−2.0 (aOR 1.41, 95% CI 0.84, 2.39) as compared to z-score >-0.5. Conclusion Preterm severe IUGR infants with z-score < −2 have an associated increased risk of PDA ligation following pharmacologic treatment as compared to normally grown infants.

Rectal Acetaminophen Improves Shunt Volume and Reduces Patent Ductus Arteriosus Ligation in Extremely Preterm Infants

Objective An alternative therapy for preterm infants with a hemodynamically significant patent ductus arteriosus (hsPDA) is needed when cyclooxygenase inhibitors fail or where treatment is contraindicated due to coexisting renal failure, necrotizing enterocolitis, and/or intestinal perforation. No studies have evaluated the efficacy of per rectum (PR) acetaminophen. The study aimed to evaluate the efficacy of PR acetaminophen in modulating the risk of PDA ligation. Study Design A retrospective matched case–control study was conducted to compare neonates born <29 weeks' gestation with evidence of hsDA, in an era when rescue rectal acetaminophen was used (January 2014–March 2018) as a treatment strategy, versus historical controls (July 2006–August 2012). All patients underwent comprehensive echocardiography assessment of ductal shunt volume according to a standardized protocol. Acetaminophen treated neonates were matched according to demographics, gestation, preintervention echocardiography features, and comorbidities. Control patients were selected when an echocardiography was performed at an equivalent postnatal age. Infants with a genetic syndrome, severe congenital malformation, or major forms of congenital heart disease excluding small atrial septal defect or ventricular septal defect, PDA, or patent formale ovale were excluded. The primary outcome was surgical ligation of the PDA. Secondary outcomes included echocardiography indices of hemodynamic significance, the composite of death, or severe BPD (defined by ventilator dependence at 36 weeks postmenstrual age). Descriptive statistics and univariate (t-tests, Fisher's exact test, and Mann–Whitney U test) analyses were used to evaluate clinical and echocardiography characteristics of the groups and compare outcomes. Results Forty infants (20 cases and 20 controls), with similar demographic and echocardiography features, were compared. Cases received 6.8 ± 0.7 days (60 mg/kg/day) of PR acetaminophen. Responders (n = 12, 60%) had echocardiography evidence of reduced ductal diameter (2.2 mm [1.9–2.6] to 1.1 mm [0–1.7], p = 0.002), left ventricular output (363 ± 108–249 ± 61 mL/min/kg; p = 0.002) and left atrium to aortic root ratio (1.7 ± 0.3–1.3 ± 0.2; p = 0.002) following treatment. The rate of PDA ligation was 50% lower (p = 0.02) and composite outcome of death or severe bronchopulmonary dysplasia was reduced (p = 0.04) in the acetaminophen group. Conclusion Rectal acetaminophen was associated with improvement in echocardiography indices of PDA shunt volume, a 50% reduction in PDA ligation rates and a reduction in the composite outcome of death or severe BPD. Pharmacologic and further prospective clinical studies are needed. Key Points

Type I and Ii Pulmonary Atresia With Intact Ventricular Septum in Infants-10-year Experience in Initial Surgery at One Center

Background: To explore the effect of initial surgery for type I and II pulmonary atresia with intact ventricular septum (PA/IVS). Methods: Patients with type I and II PA/IVS undergoing initial surgery were enrolled, including type I with systemic to pulmonary (BT) shunt+patent ductus arteriosus (PDA) ligation+mosaic surgery (surgical A), BT shunt+PDA ligation+pulmonary valve incision without extracorporeal circulation (surgical B), type II with BT shunt+PDA ligation+right ventricular outflow tract (RVOT) incision+transpulmonary annulus patch (TP) (surgical C), and BT shunt+PDA ligation+RVOT incision+TP+artificial pulmonary valve (surgical D). Mechanical ventilation time (MVT), length of ICU stay, mortality rate, tricuspid Z value (TZ), tricuspid regurgitation (TR), McGoon ratio, oxygen saturation (SpO2), pulmonary transvalvular pressure (PTP), pulmonary regurgitation (PR), survival rate and re-operation rate were compared between surgical A and B, and between surgical C and D.Results: After surgery, PR was greater by surgical A than by surgical B at 1 month (P<0.05); lower TZ and McGoon ratio and greater PR, PTP and TR at 3 months (P<0.05); lower SpO2 (P<0.05), greater PTP at 6 months (P<0.01); greater TR and PTP at 1 year (P<0.05). MVT and length of ICU stay were longer by surgical C than by surgical D (P<0.05). There was greater PR at discharge and 1 month (P<0.01); greater TR and PR, lower McGoon ratio and SpO2 at 3 months (P<0.05); lower TZ and PTP and greater PR and PTP at 6 months (P<0.05) and 1 year (P<0.01) respectively.Conclusion: Surgical B and D are superior to surgical A and C respectively.

Vocal cord palsy as a sequela of paediatric cardiac surgery – a review

Background: Vocal cord palsy is one of the recognised complications of complex cardiac surgery in the paediatric population. While there is an abundance of literature highlighting the presence of this complication, there is a scarcity of research focusing on the pathophysiology, presentation, diagnosis, and treatment options available for children affected by vocal cord palsy. Materials and methods: Electronic searches were conducted using the search terms: “Vocal Cord Palsy,” “VCP,” “Vocal Cord Injury,” “Paediatric Heart Surgery,” “Congenital Heart Surgery,” “Pediatric Heart Surgery,” “Vocal Fold Movement Impairment,” “VFMI,” “Vocal Fold Palsy,” “PDA Ligation.” The inclusion criteria were any articles discussing the outcomes of vocal cord palsy following paediatric cardiac surgery. Results: The two main populations affected by vocal cord palsy are children undergoing aortic arch surgery or those undergoing PDA ligation. There is paucity of prospective follow-up studies; it is therefore difficult to reliably assess the current approaches and the long-term implications of management options. Conclusion: Vocal cord palsy can be a devastating complication following cardiac surgery, which if left untreated, could potentially result in debilitation of quality of life and in severe circumstances could even lead to death. Currently, there is not enough high-quality evidence in the literature to aid recognition, diagnosis, and management leaving clinicians to extrapolate evidence from adult studies to make clinical judgements. Future research with a focus on the paediatric perspective is necessary in providing evidence for good standards of care.

Ductal ligation timing and neonatal outcomes: a 12-year bicentric comparison

Patent ductus arteriosus (PDA) is common among extremely preterm infants. In selected cases, surgical PDA ligation may be required. The timing for PDA ligation may depend upon a variety of factors, with potential clinical implications. We aimed to investigate the impact of different surgical PDA managements on ligation timing and neonatal outcomes. Inborn infants < 32 weeks of gestation and < 1500 g admitted at two tertiary Neonatal Intensive Care Units that underwent PDA ligation between 2007 and 2018 were enrolled in this retrospective cohort study and split into the following groups based on their surgical management: on-site bedside PDA ligation (ONS) vs. referral to an off-site pediatric cardiac surgery (OFS). Neonatal characteristics, surgical timing, and clinical outcomes of the enrolled infants were compared between the groups. Multivariate analysis was performed to evaluate the impact of PDA ligation timing on significantly different outcomes. Seventy-eight neonates (ONS, n = 39; OFS, n = 39) were included. Infants in the ONS group underwent PDA ligation significantly earlier than those in the OFS group (median age 12 vs. 36 days, p < 0.001) with no increase in postoperative mortality and complications. The multivariate analysis revealed a significant association between PDA ligation timing, late-onset sepsis prevalence (OR 1.045, 0.032), and oxygen need at discharge (OR 1.037, p = 0.025).Conclusions: Compared with off-site surgery, on-site bedside ligation allows an earlier surgical closure of PDA, with no apparent increase in mortality or complications. Earlier PDA ligation may contribute to reduced rates of late-onset sepsis and post-discharge home oxygen therapy, with possible cost-benefit implications. What is known:• Ineffective or contraindicated pharmacological closure of a hemodynamically significant PDA may require a surgical ligation.• Available literature comparing the effect of early vs. late PDA ligation on the main neonatal morbidities has yield contrasting results. What is new:• The availability of a cardiac surgery service performing bedside PDA ligation allows an earlier intervention compared to patient referral to an off-site center, with no difference in postoperative mortality and complications compared to off-site surgery.• Earlier PDA ligation was associated with a lower prevalence of late-onset sepsis and of oxygen need at discharge, with possible cost-benefit implications.

Recorded Flexible Nasolaryngoscopy for Neonatal Vocal Cord Assessment in a Prospective Cohort

Objective: Assessing vocal cord mobility by flexible nasolaryngoscopy (FNL) can be difficult in neonates. To date, prospective studies evaluating the incidence and diagnostic accuracy of vocal cord paralysis (VCP) after surgical patent ductus arteriosus (PDA) ligation are limited. It is unknown whether video FNL improves diagnosis in this population. This study compared video recordings with bedside evaluation for diagnosis of VCP and determined inter-rater reliability of the diagnosis of VCP in preterm infants after PDA ligation. Methods: Prospective cohort of preterm neonates undergoing bedside FNL within two weeks of extubation following PDA ligation. In a subset, FNL was recorded. Two pediatric otolaryngologists, blinded to the initial diagnosis, reviewed the FNL video recordings. Results: Eighty infants were enrolled and 37 with a recorded FNL were included in the cohort. Average gestational age at birth was 25.2 weeks (SD: 1.2) and postmenstrual age at FNL was 37.0 weeks (SD: 4.5), which was 9.5 days (SD: 14.7) after extubation following PDA repair. There were 6 diagnosed with left VCP (16.2%; 95% CI: 4.3-28.1%) at bedside, and 9 diagnosed by video review (24.3%; 95% CI: 10.5-38.1%) ( P = .56). Videos confirmed all 6 VCP diagnosed initially, but also identified 3 additional cases. Though imperfect, reviewing FNL by video showed substantial reliability (kappa = .75), with 91.9% agreement. Conclusion: Video recorded FNL most often confirms a bedside diagnosis of VCP, but may also identify discrepancies. Physicians should consider the limitations of diagnosis especially when infants persist with symptoms such as weak voice or signs of postoperative aspiration. Level of Evidence 2b

Thoracic Endovascular Aortic Repair for Pseudoaneurysms After Repair of Patent Ductus Arteriosus

Background: Pseudoaneurysms that develop after surgical repair of a patent ductus arteriosus (PDA) are more likely to rupture, but open surgery including a repeat thoracotomy would be highly invasive. We report 2 cases of thoracic endovascular aortic repair (TEVAR) for such pseudoaneurysms. Methods/Results: A 59-year-old woman who underwent PDA surgical ligation at 13 years of age presented with sudden hemoptysis. She was diagnosed with a ruptured distorted pseudoaneurysm sized 26 mm; emergency TEVAR was performed. A 23-year-old woman with a history of Down syndrome, endocardial cushion defect, and PDA underwent 2 thoracotomy surgeries including PDA ligation. During a medical checkup, an abnormal shadow was detected on chest radiography. She was diagnosed with a 15-mm pseudoaneurysm after PDA surgical repair; TEVAR was performed. In both cases, the postoperative course was uneventful. Conclusions: To the best of our knowledge, this is the first report of emergency TEVAR for ruptured pseudoaneurysms after PDA ligation. Thoracic endovascular aortic repair is an important therapeutic option for such cases as it eliminates the need for repeat thoracotomy.