Application of Video Laryngoscopy for Minimally Invasive Surfactant Therapy: A Retrospective Comparative Cohort Study.

Minimally invasive surfactant therapy (MIST) has emerged as a preferred method of surfactant delivery. Pioneers of this technique have described the use of direct laryngoscopy (DL) for MIST. With the increasing application of video laryngoscopy (VL) for neonatal airway management, it is speculated that MIST techniques can be adapted for use with VL. OBJECTIVE: To compare procedural success, operator ease of use, and complication of MIST using VL vs. MIST using DL. METHODS: This was a retrospective, observational cohort study conducted at a tertiary-level neonatal intensive care unit after obtaining ethical approval. We included neonates who received MIST between 1 October 2020 and 31 October 2022. Baseline demographic characteristics, along with procedural data, were collected. Primary outcome measures included the overall procedural success rate, the need for multiple attempts, and the total number of attempts. Secondary outcome measures included the occurrence of adverse events, the need for a second dose of surfactant, and the need for intubation within 7 days of the procedure. Means and SDs, independent t-tests, frequencies, and chi-square were used as appropriate. p-values < 0.05 were considered statistically significant. RESULTS: Of the 79 neonates included, 37 neonates received MIST via VL, while 42 received MIST via DL. The median gestational age was lower in the VL group at 29.0 weeks vs. 30.5 weeks (p = 0.011) in the DL group. The median birthweight in the VL group was 1260 g, IQR (1080, 1690), which was significantly lower than the DL group, which was 1575 g, IQR (1220, 2251), p = 0.028. Purpose-built catheter use was higher in the DL group. The overall procedural success was similar between groups. The need for multiple attempts was lower with VL in comparison to DL [4 (11%) vs. 13 (31%); p = 0.034)] at the univariate level but not significant at multivariate analysis (p = 0.131). Procedural complications, the need for a second dose of surfactant, the need for mechanical ventilation post-MIST, and operator ease of use were similar. User comments emphasized the value of VL in providing real-time visual information to confirm catheter placement and guide operators/trainees. CONCLUSION: Overall, in our cohort, despite VL being a more recently adapted technology used more in smaller, sicker, and more premature neonates, procedural success, complications, and operator ease of use for MIST using VL and DL were comparable. Our findings show the successful application of VL for MIST and suggest procedural advantages that might facilitate universal adoption.

Altered resting-state functional connectivity in newborns with hypoxic ischemic encephalopathy assessed using high-density functional near-infrared spectroscopy.

Hypoxic-ischemic encephalopathy (HIE) results from a lack of oxygen to the brain during the perinatal period. HIE can lead to mortality and various acute and long-term morbidities. Improved bedside monitoring methods are needed to identify biomarkers of brain health. Functional near-infrared spectroscopy (fNIRS) can assess resting-state functional connectivity (RSFC) at the bedside. We acquired resting-state fNIRS data from 21 neonates with HIE (postmenstrual age [PMA] = 39.96), in 19 neonates the scans were acquired post-therapeutic hypothermia (TH), and from 20 term-born healthy newborns (PMA = 39.93). Twelve HIE neonates also underwent resting-state functional magnetic resonance imaging (fMRI) post-TH. RSFC was calculated as correlation coefficients amongst the time courses for fNIRS and fMRI data, respectively. The fNIRS and fMRI RSFC maps were comparable. RSFC patterns were then measured with graph theory metrics and compared between HIE infants and healthy controls. HIE newborns showed significantly increased clustering coefficients, network efficiency and modularity compared to controls. Using a support vector machine algorithm, RSFC features demonstrated good performance in classifying the HIE and healthy newborns in separate groups. Our results indicate the utility of fNIRS-connectivity patterns as potential biomarkers for HIE and fNIRS as a new bedside tool for newborns with HIE.

Shape of Pulmonary Artery Doppler Flow Profile and Right Ventricular Hemodynamics in Neonates.

OBJECTIVES: To characterize pulmonary artery Doppler flow profile (PAFP) patterns among infants receiving care in neonatal intensive care units and to examine the association of PAFP patterns with pulmonary and right ventricular (RV) hemodynamics. STUDY DESIGN: This is a retrospective study at 2 tertiary intensive care units over 4 years that included neonates who demonstrated a complete tricuspid regurgitation envelope on targeted neonatal echocardiography. Separate personnel reviewed TNEs to characterize PAFP patterns, divide cohort into PAFP groups, and measure quantitative indices of RV hemodynamics (RV systolic pressure, pulmonary artery acceleration time and its ratio with RV ejection time, tricuspid annular plane systolic excursion, and RV output), for intergroup comparisons. RESULTS: We evaluated TNEs from 186 neonates with median gestational age of 28.5 weeks (IQR, 25.9-35.9 weeks). Four distinct PAFP patterns were identified (A) near-isosceles triangle (22%), (B) right-angled triangle (29%), (C) notching (40%), and (D) low peak velocity (<0.4 m/s; 9%). Groups A-C demonstrated a stepwise worsening in all indices of PH, whereas pattern D was associated with lower tricuspid annular plane systolic excursion and RV output. Using common definitions of pulmonary hypertension (PH), pattern A performed best to rule out PH (sensitivity range, 81%-90%) and pattern C for diagnosing PH (specificity range, 63%-78%). CONCLUSIONS: Inspection of PAFP is a simple bedside echocardiography measure that provides clinically meaningful information on underlying RV hemodynamics and may aid in screening and monitoring of patients for PH in intensive care units.

Purpose Built Catheters for Minimally Invasive Surfactant Therapy: Experience from a Canadian Tertiary Level Neonatal Intensive Care Unit.

Background: Minimally invasive surfactant therapy (MIST), a method of surfactant delivery via a thin catheter during spontaneous breathing, is an increasingly popular alternative to intubation and surfactant administration. Recently, purpose-built catheters for MIST received regulatory approval in Canada and became available for use. However, procedural success and user experience with such catheters have not been described. Methods: This retrospective cohort study included neonates who received MIST using purpose-built catheters between January 1, 2021, and March 31, 2022. Two types of purpose-built catheters were used in this period - SurfCath™ and BLEScath™. Procedural success, number of attempts, and adverse events in neonates receiving MIST via the two catheters were compared using chi-square or Fisher's tests. User experience was described using an ease-of-use scale. Results: Thirty-seven neonates met eligibility criteria; 22 received MIST via SurfCath™, whereas 15 received MIST via BLEScath™. Success rates were 91% in SurfCath™ and 93% in BLEScath™ (P> 0.994). Failed attempts were lower in SurfCath™ (23%) in comparison to BLEScath™ (33%), but the difference was not statistically significant (P=0.708). Among operators, 90% found SurfCath™ very easy/relatively easy to use compared to 43% of users reflecting the same degree of use with BLEScath™ (P=.021). There was no difference in adverse events. Conclusion: This is the first study in Canada to report MIST with purpose-built catheters. Overall, the success rate was equally high with both catheters. Users subjectively reported higher ease of use with SurfCath™. Commercially available purpose-built catheters should facilitate universal adaptation of the MIST method.

Impact of Targeted Neonatal Echocardiography on Patent Ductus Arteriosus Management in a Canadian Tertiary Care Neonatal Unit: A Retrospective Cohort Study.

OBJECTIVE: Comprehensive assessment of hemodynamic significance of a patent ductus arteriosus (PDA) is a common indication to perform targeted neonatal echocardiography (TNE). Impact of implementation of such an assessment on PDA management decisions remains to be reported. The objective of this study is to compare PDA-related hemodynamic information and PDA treatment decisions before and after introduction of TNE service. STUDY DESIGN: This was a retrospective cohort study at a tertiary level neonatal intensive care unit in Southwestern Ontario. We investigated two time periods: Epoch-1 (non-TNE 2013-2016) versus Epoch-2 (TNE 2018-2021). We included neonates < 32 weeks with PDA. Data on baseline clinical characteristics, PDA-related echocardiographic parameters, PDA treatment details, and relevant long-term outcomes were collected. Primary outcome was defined as PDA treatment rates and need for multiple courses. Secondary outcomes included availability of PDA hemodynamic data and neonatal mortality/morbidity (PDA-related) RESULTS: A total of 275 neonates were included. A total of 162 were assessed by conventional echocardiography in Epoch-1, whereas 113 were assessed by TNE in Epoch-2. Baseline clinical characteristics were similar. Epoch-2 had more echocardiographic assessments per patient of 2.7 (±1.8) versus 1.9 (± 1.3), p < 0.001 in Epoch1. The mean postnatal age at first echocardiographic assessment was higher in Epoch-2 (12.7 days [ ± 14.6]) than in Epoch-1 (7.9 days [ ± 10.4]), p < 0.001. Comprehensive hemodynamic assessment of PDA-related echocardiographic parameters such as PDA size, shunt pattern, effect on systemic circulation, and pulmonary circulation were higher in Epoch-2. Overall, PDA treatment rates were comparable in the two time periods. The use of multiple courses of treatment was higher in Epoch-1 than in Epoch-2 (47.8 vs. 31.7%, p = 0.047). In Epoch-1, neonates received PDA treatment earlier than in Epoch-2. CONCLUSION: With the implementation of the TNE service, increased echocardiographic evaluations per patient were completed with availability of more comprehensive hemodynamic information about PDA. PDA treatment rates were similar in the two epochs, but need for multiple courses were less in TNE era. KEY POINTS: · TNE allows comprehensive hemodynamic assessment of PDA.. · Implementation of dedicated TNE service led to increased use of echocardiography to assess PDA.. · Standardized hemodynamic assessment of PDA may allow improved individualization of treatment need..

Subcortical brain volumes in neonatal hypoxic-ischemic encephalopathy.

BACKGROUND: Despite treatment with therapeutic hypothermia, hypoxic-ischemic encephalopathy (HIE) is associated with adverse developmental outcomes, suggesting the involvement of subcortical structures including the thalamus and basal ganglia, which may be vulnerable to perinatal asphyxia, particularly during the acute period. The aims were: (1) to examine subcortical macrostructure in neonates with HIE compared to age- and sex-matched healthy neonates within the first week of life; (2) to determine whether subcortical brain volumes are associated with HIE severity. METHODS: Neonates (n = 56; HIE: n = 28; Healthy newborns from the Developing Human Connectome Project: n = 28) were scanned with MRI within the first week of life. Subcortical volumes were automatically extracted from T1-weighted images. General linear models assessed between-group differences in subcortical volumes, adjusting for sex, gestational age, postmenstrual age, and total cerebral volumes. Within-group analyses evaluated the association between subcortical volumes and HIE severity. RESULTS: Neonates with HIE had smaller bilateral thalamic, basal ganglia and right hippocampal and cerebellar volumes compared to controls (all, p < 0.02). Within the HIE group, mild HIE severity was associated with smaller volumes of the left and right basal ganglia (both, p < 0.007) and the left hippocampus and thalamus (both, p < 0.04). CONCLUSIONS: Findings suggest that, despite advances in neonatal care, HIE is associated with significant alterations in subcortical brain macrostructure. IMPACT: Compared to their healthy counterparts, infants with HIE demonstrate significant alterations in subcortical brain macrostructure on MRI acquired as early as 4 days after birth. Smaller subcortical volumes impacting sensory and motor regions, including the thalamus, basal ganglia, and cerebellum, were seen in infants with HIE. Mild and moderate HIE were associated with smaller subcortical volumes.

Can ventricular 3D ultrasound of neonates with posthemorrhagic hydrocephalus inform on the need for a ventriculoperitoneal shunt?

OBJECTIVE: Some neonates born prematurely with intraventricular hemorrhage develop posthemorrhagic hydrocephalus and require lifelong treatment to divert the flow of CSF. Early prediction of the eventual need for a ventriculoperitoneal shunt (VPS) is difficult, and early discussions with families are based on statistics and the grade of hemorrhage. The authors hypothesize that change in ventricular volume during ventricular taps that is measured with repeated 3D ultrasound (3D US) imaging of the lateral ventricles could be used to assess the risk of the future requirement of a VPS. METHODS: A total of 92 neonates with intraventricular hemorrhage who were treated in the NICU were recruited between April 2012 and November 2019. Only patients who required ventricular taps (VTs) were included in this study, resulting in the analysis of 19 patients with a total of 61 VTs. Among them, 14 patients were treated with a VPS, and in 5 patients the hydrocephalus resolved spontaneously. Parameters studied were total ventricular volume measured with 3D US, ventricular volume change after VT, the ratio between volume reduction and tap amount, the difference between tap amount and volume reduction after tap, the average tap amount, the average number of days between taps, pre-tap head circumference, and reduction in head circumference after tap. RESULTS: Statistically significant differences were found in ventricular volume reduction after tap (p = 0.007), the ratio between volume reduction and tap amount (p = 0.03), the difference between tap amount and volume reduction after tap (p = 0.05), and the interval of days between taps (p = 0.0115). CONCLUSIONS: Measuring with 3D US before and after VT can be a useful tool for quantifying ventricular volume. The findings in this study showed that neonates who experience a large reduction of ventricular volume after VT are more likely to be treated with a shunt than are neonates who experience a small reduction.

Impact of Catheter Choice on Procedural Success of Minimally Invasive Surfactant Therapy.

OBJECTIVE: Surfactant delivery via a thin endotracheal catheter during spontaneous breathing; a technique called minimally invasive surfactant therapy (MIST) is an alternative to intubation and surfactant administration. Procedural details among different centers vary, with marked differences in the choice of catheter to instill surfactant. Studies report use of feeding catheters, multiaccess suction catheters, vascular catheters, and more recently custom-built catheters for this purpose. The impact of choice of catheter on procedural success and procedural adverse effects has not been reported. Our present study compares the procedural success and adverse effects of MIST using a semirigid vascular catheter (16G Angiocath-Hobart Method) versus a flexible multiaccess catheter (MAC). STUDY DESIGN: This was a retrospective review of prospectively collected data at a tertiary care neonatal intensive care unit in Southwestern Ontario. All neonates who received surfactant via MIST between May 1, 2016 and September 30, 2020 were included in the study. Relevant baseline characteristics and data on procedural details (premedication, type of catheter, etc.) were collected. The procedural success, number of attempts, and adverse effects between neonates who received MIST via MAC and 16G Angiocath was compared by using Chi-square test or Fisher's test as appropriate. A p-value of less that 0.05 was considered significant. RESULTS: A total of 139 neonates received surfactant via MIST method during the study period. Moreover, 93 neonates received the surfactant via MAC, while 46 received it via Angiocath. The baseline demographic characteristics in the two group were similar. A higher proportion of neonates in Angiocath group received Atropine (100 vs. 76%, p = 0.002) and Fentanyl (98 vs. 36%, p < 0.001) than the MAC group.The procedural success was 91% in the Angiocath group and 89% in the MAC group (p > 0.99). Multiple attempts were needed in 24% of neonates in the Angiocath group and 37% in the MAC group (p = 0.158). More episodes of desaturations were noted in the Angiocath group (89%) than the MAC group (69%; p = 0.012). Other rates of common adverse effects were similar between the two groups. On exploratory analysis fentanyl use held significant association with less success, more desaturation, apneic episodes, and need of positive pressure ventilation /intubation. CONCLUSION: The overall procedural success of MIST is similar in both catheter groups. The proportion of neonates requiring multiple attempts was lower with the Angiocath, though difference was not statistically significant. Desaturation episodes were seen more frequently in the Angiocath group, which was related to higher use of procedural sedation in this group. KEY POINTS: · MIST is emerging as a less invasive method of surfactant delivery that has proven clinical benefits.. · Considerable, procedural variation is reported, particularly regarding choice of catheter.. · Our present study compares the procedural success and adverse effects of MIST using a semirigid vascular catheter (16G Angiocath-Hobart method) versus a flexible MAC.. · High and comparable procedural success was seen in both groups..

Road to a rare diagnosis: Description of novel unbalanced translocation causing partial trisomy 17p.

Trisomy 17 is a rare chromosomal disorder. Existing literature on the topic is limited and mostly refer to mosaic Trisomy 17 cases. Our report summarizes the 70-day clinical course of a late preterm neonate with partial Trisomy 17p karyotype 46,XY,der(14)t(14;17)(p11.1;p11.2) dpat. Trisomy 17 due to unbalanced translocation is rare, and our case elaborates the clinical presentation with intestinal malfunction without any anatomical pathology and urethral diverticulum and the ethical dilemma in decision-making. The male proband was born at 35 weeks with antenatal findings of multiple neurological and other abnormalities such as cystic hygroma, absent corpus collosum, high riding third ventricle, absent cavum septum pellucidum, indented occiput, absent ductus venous, and intrauterine growth restriction. The postnatal findings included significant facial dysmorphisms with short palpebral fissures, hypertelorism, low set ears, micrognathia, hirsutism, and single palmar creases, central hypotonia, and hyperreflexia of upper limbs bilaterally. Genital-urinary assessment revealed a urinary diverticulum and significantly underdeveloped scrotum with undescended testes. Infant had excessive irritability and resistance to sleep despite increasing doses of analgesia and sedation, and persistent respiratory and feeding difficulties. Enteral nutrition could not be established due to profuse and persistent diarrhea, necessitating use of total parenteral nutrition. Microarray assay exhibited a pathogenic copy number gain of approximately 21.4 Mb of chromosome region 17p13.3p11.2. Follow-up chromosome analysis and FISH revealed an abnormal male karyotype with a derivative chromosome 14, resulting from an unbalanced translocation between the short arm of one chromosome 14 and the short arm of one chromosome 17, effectively resulting in trisomy 17p11.2. It was derived from a paternal balanced t(14;17)(p11.1;p11.2) as shown by chromosome analysis and FISH studies. The rarity of this chromosomal disorder contributed to difficulty with prognosis and led to bioethical dilemma regarding life-sustaining measures and quality of life. Through shared decision-making processes and in consideration of poor prognosis, parents decided to withdraw life-sustaining care and the proband died at postnatal day of life 70.

A survey of minimally invasive surfactant therapy in Canada.

Introduction: Minimally invasive surfactant therapy (MIST) can be used to treat neonatal respiratory distress syndrome in neonatal intensive care units (NICUs). Clinical and institutional variances in MIST utilization persist globally with little published research regarding MIST utilization in Canada. Therefore, the objective of this study was to survey MIST utilization in NICUs in Canada. Methods: An online survey was emailed to the 33 participating centres of Canadian Neonatal NetworkTM (CNN) Evidence-based Practice for Improving Quality (EPIQ) Lung Health Group (LHG). Site demographics and surfactant therapy procedural details were categorically collected. Free text and multiple-choice questions were utilized to capture perceived barriers and individual preferences for MIST use. Results: Twenty-eight of 33 participating members of the CNN EPIQ-LHG completed the survey between April 2021 and October 2021 (85%); 17/28 (61%) respondents reported ongoing MIST utilization at their center. Most centers that used MIST techniques administered bovine lipid extract surfactant (68%), commonly using angiocatheters (47%) and purpose-built catheters (41%). MIST was widely used for patients at 26-33 weeks gestational age (88%). Nine centres had never used MIST (32%), and 3 indicated a plan to implement MIST within the next 2 years. Common barriers to MIST use included lack of consensus amongst clinicians (78%), lack of training (56%), and lack of experience with MIST (56%). Conclusion: While MIST is being increasingly used in Canadian NICUs, universal use is yet to be seen. Clinician inexperience and lack of consensus, formal training, and local guidelines contribute to underutilization of MIST. Training workshops, country-wide data collection, and uniform operating protocols are needed to standardize practice.

Educational Impact of Targeted Neonatal Echocardiography and Hemodynamics Programs on Neonatal-Perinatal Medicine Fellows.

OBJECTIVE: Targeted neonatal echocardiography (TNE) is a real-time cardiac imaging modality used by a hemodynamics program to aid in diagnosis, treatment, and monitoring of neonatal cardiovascular illness. This study aimed to describe trainees' perspectives on existing hemodynamics education and perceived impacts of TNE and hemodynamics services on their education. STUDY DESIGN: This was a mixed quantitative and qualitative study that surveyed neonatal-perinatal medicine (NPM) fellow trainees in Canada and the United States, at programs both with and without a hemodynamics service. RESULTS: Ninety-two fellows responded to the survey, of whom 24 (26%) were enrolled in a program with an active hemodynamics service, 64 (70%) were training at a program without a hemodynamics service, and 4 (4%) were unsure. Trainees at centers with a hemodynamics service were more satisfied with their cardiovascular physiology education (91 vs. 69%, p = 0.040). Twenty-five percent of all trainees felt they do not have sufficient hemodynamics training to prepare them for independent practice. Areas of knowledge gaps were identified. Bedside teaching combined with didactic teaching was identified as useful means of teaching. CONCLUSION: Most trainees believed that TNE and a hemodynamics service are valuable educational assets. Thoughtful curriculum design for real-time and consolidation learning, with specific emphasis on content gaps, should be considered. KEY POINTS: · NPM Fellows perceive TNE & Neonatal Hemodynamics service as a valuable educational opportunity.. · Incorporation of TNE/Hemodynamics teaching into NPM curriculum can enrich trainee experience.. · Combining bedside and classroom teaching is key to successful cardiovascular training..

Assessing cerebral blood flow, oxygenation and cytochrome c oxidase stability in preterm infants during the first 3 days after birth.

A major concern with preterm birth is the risk of neurodevelopmental disability. Poor cerebral circulation leading to periods of hypoxia is believed to play a significant role in the etiology of preterm brain injury, with the first three days of life considered the period when the brain is most vulnerable. This study focused on monitoring cerebral perfusion and metabolism during the first 72 h after birth in preterm infants weighing less than 1500 g. Brain monitoring was performed by combining hyperspectral near-infrared spectroscopy to assess oxygen saturation and the oxidation state of cytochrome c oxidase (oxCCO), with diffuse correlation spectroscopy to monitor cerebral blood flow (CBF). In seven of eight patients, oxCCO remained independent of CBF, indicating adequate oxygen delivery despite any fluctuations in cerebral hemodynamics. In the remaining infant, a significant correlation between CBF and oxCCO was found during the monitoring periods on days 1 and 3. This infant also had the lowest baseline CBF, suggesting the impact of CBF instabilities on metabolism depends on the level of blood supply to the brain. In summary, this study demonstrated for the first time how continuous perfusion and metabolic monitoring can be achieved, opening the possibility to investigate if CBF/oxCCO monitoring could help identify preterm infants at risk of brain injury.

Does the Head Position Affect Neonatal Lateral Ventricular Volume?

OBJECTIVE: This study aimed to determine whether there are differences in the lateral ventricular volumes, measured by three-dimensional ultrasound (3D US) depending on the posture of the neonate (right and left lateral decubitus). STUDY DESIGN: This was a prospective analysis of the lateral ventricular volumes of preterm neonates recruited from Victoria Hospital, London, Ontario (June 2018-November 2019). A total of 24 premature neonates were recruited. The first cohort of 18 unstable premature neonates were imaged with 3D US in their current sides providing 15 right-sided and 16 left-sided 3D US images. The neonates in the second cohort of six relatively stable infants were imaged after positioning in each lateral decubitus position for 30 minutes, resulting in 40 3D US images obtained from 20 posture change sessions. The images were segmented and the ventricle volumes in each lateral posture were compared with determine whether the posture of the head influenced the volume of the upper and lower ventricle. RESULTS: For the first cohort who did not have their posture changed, the mean of the right and left ventricle volumes were 23.81 ± 15.51 and 21.61 ± 16.19 cm3, respectively, for the 15 images obtained in a right lateral posture and 13.96 ± 8.69 and 14.92 ± 8.77 cm3, respectively, for the 16 images obtained in the left lateral posture. Similarly, for the second cohort who had their posture changed, the mean of right and left ventricle volumes were 20.92 ± 17.3 and 32.74 ± 32.33 cm3, respectively, after 30 minutes in the right lateral posture, and 21.25 ± 18.4 and 32.65 ± 31.58 cm3, respectively, after 30 minutes in the left lateral posture. Our results failed to show a statistically significant difference in ventricular volumes dependence on posture. CONCLUSION: Head positioned to any lateral side for 30 minutes does not have any effect on the lateral ventricular volumes of neonates. KEY POINTS: · Three-dimensional cranial ultrasound can measure neonatal ventricle volume.. · Ventricle volume in each lateral ventricle may be affected by posture of the neonate.. · The 30 minutes in any lateral posture is not sufficient to create volume difference in lateral ventricles..

Airway injury and pneumomediastinum associated with less invasive surfactant administration in a premature neonate: a case report.

BACKGROUND: The use of less invasive surfactant administration (LISA)/minimally invasive surfactant therapy (MIST) has increased due to its potential advantage over traditional surfactant delivery methods through an endotracheal tube. Known complications for this procedure include failure of the first attempt at insertion, desaturation, and bradycardia. To the best of our knowledge, this is the first reported case of pneumomediastinum and subcutaneous emphysema following LISA. CASE PRESENTATION: A preterm newborn born at 27 weeks of gestation presented with respiratory distress syndrome requiring surfactant replacement. LISA using the Hobart method was completed. There was a report of procedural difficulty related to increased resistance to insertion of the 16G angiocath. The newborn was subsequently noted to have subcutaneous emphysema over the anterior aspect of the neck and substantial pneumomediastinum on radiological assessment. Associated complications included hypotension requiring inotropic support. The newborn was successfully managed conservatively, with complete resolution of the air leak. CONCLUSIONS: Upper airway injury leading to air leak syndrome is a rare complication of the Hobart method for LISA. Awareness of such procedural complications is important as the use of the LISA method increases.

Use of combination therapy with acetaminophen and ibuprofen for closure of the patent ductus arteriosus in preterm neonates.

OBJECTIVE: To compare effectiveness and safety of combination therapy (acetaminophen and ibuprofen) to monotherapy (ibuprofen, indomethacin, or acetaminophen alone) in treatment of the patent ductus arteriosus (PDA) in premature neonates. METHODS: This was a retrospective cohort study of neonates admitted to a tertiary-level neonatal intensive care unit. Included neonates were born at <32 weeks gestation and received pharmacotherapy for PDA closure. Based on the primary therapy received, our cohort was divided into the following four groups: indomethacin alone, ibuprofen alone, acetaminophen alone, and ibuprofen and acetaminophen (in combination). Baseline characteristics, effectiveness, safety, neonatal mortality, and morbidities rates between these groups were compared. RESULTS: One hundred and forty neonates were analyzed; 17 received combination therapy, and 123 neonates received monotherapy: 22 (17.9%) ibuprofen, 29 (23.6%) acetaminophen, and 72 (58.5%) indomethacin. The PDA closure rates were 41.7% for indomethacin, 41.2% for combination therapy, 37.9% for acetaminophen, and 31.8% for ibuprofen (P=0.100). Rates of adverse effects were comparable between the groups. CONCLUSION: The rate of ductal closure was not different between combination therapy and monotherapy. The study did not demonstrate any increased adverse effects in the combination group. Future well-designed prospective clinical trials are needed to guide clinical practice.

Relative effectiveness and safety of pharmacotherapeutic agents for patent ductus arteriosus (PDA) in preterm infants: a protocol for a multicentre comparative effectiveness study (CANRxPDA).

INTRODUCTION: Patent ductus arteriosus (PDA) is the most common cardiovascular problem that develops in preterm infants and evidence regarding the best treatment approach is lacking. Currently available medical options to treat a PDA include indomethacin, ibuprofen or acetaminophen. Wide variation exists in PDA treatment practices across Canada. In view of this large practice variation across Canadian neonatal intensive care units (NICUs), we plan to conduct a comparative effectiveness study of the different pharmacotherapeutic agents used to treat the PDA in preterm infants. METHODS AND ANALYSIS: A multicentre prospective observational comparative-effectiveness research study of extremely preterm infants born <29 weeks gestational age with an echocardiography confirmed PDA will be conducted. All participating sites will self-select and adhere to one of the following primary pharmacotherapy protocols for all preterm babies who are deemed to require treatment.Standard dose ibuprofen (10 mg/kg followed by two doses of 5 mg/kg at 24 hours intervals) irrespective of postnatal age (oral/intravenous).Adjustable dose ibuprofen (oral/intravenous) (10 mg/kg followed by two doses of 5 mg/kg at 24 hours intervals if treated within the first 7 days after birth. Higher doses of ibuprofen up to 20 mg/kg followed by two doses of 10 mg/kg at 24 hours intervals if treated after the postnatal age cut-off for lower dose as per the local centre policy).Acetaminophen (oral/intravenous) (15 mg/kg every 6 hours) for 3-7 days.Intravenous indomethacin (0.1-0.3 mg/kg intravenous every 12-24 hours for a total of three doses). OUTCOMES: The primary outcome is failure of primary pharmacotherapy (defined as need for further medical and/or surgical/interventional treatment following an initial course of pharmacotherapy). The secondary outcomes include components of the primary outcome as well as clinical outcomes related to response to treatment or adverse effects of treatment. SITES AND SAMPLE SIZE: The study will be conducted in 22 NICUs across Canada with an anticipated enrollment of 1350 extremely preterm infants over 3 years. ANALYSIS: To examine the relative effectiveness of the four treatment strategies, the primary outcome will be compared pairwise between the treatment groups using χ2 test. Secondary outcomes will be compared pairwise between the treatment groups using χ2 test, Student's t-test or Wilcoxon rank sum test as appropriate. To further examine differences in the primary and secondary outcomes between the four groups, multiple logistic or linear regression models will be applied for each outcome on the treatment groups, adjusted for potential confounders using generalised estimating equations to account for within-unit-clustering. As a sensitivity analysis, the difference in the primary and secondary outcomes between the treatment groups will also be examined using propensity score method with inverse probability weighting approach. ETHICS AND DISSEMINATION: The study has been approved by the IWK Research Ethics Board (#1025627) as well as the respective institutional review boards of the participating centres. TRIAL REGISTRATION NUMBER: NCT04347720.