Dopamine or norepinephrine for sepsis-related hypotension in preterm infants: a retrospective cohort study.

The purpose of this study is to compare the clinical effectiveness of dopamine (DA) versus norepinephrine (NE) as first-line therapy for sepsis-related hypotension in preterm infants. This is a retrospective cohort study over 10 years at two tertiary neonatal units. Preterm infants born < 35 weeks post-menstrual age (PMA), who received DA or NE as primary therapy for hypotension during sepsis, defined as culture-positive or culture-negative infections or necrotizing enterocolitis (NEC), were included. Episode-related mortality (< 7 days from treatment), pre-discharge mortality, and major morbidities among survivors were compared between two groups. Analyses were adjusted using the inverse probability of treatment weighting estimated by propensity score (PS). A total of 156 infants were included, 113 received DA and 43 NE. The mean ± SD PMA at birth and at treatment for the DA and NE groups were 25.8 ± 2.3 vs. 25.2 ± 2.0 weeks and 27.7 ± 3.0 vs. 27.1 ± 2.6 weeks, respectively (p > 0.05). Pre-treatment, the NE group had higher mean airway pressure (14 ± 4 vs. 12 ± 4 cmH2O), heart rate (185 ± 17 vs. 175 ± 17 beats per minute), and median (IQR) fraction of inspired oxygen [0.67 (0.42, 1.0) vs. 0.52 (0.32, 0.82)] (p < 0.05 for all). After PS adjustment, NE was associated with lower episode-related mortality [adjusted odds ratio (95% CI) 0.55 (0.33, 0.92)], pre-discharge mortality [0.60 (0.37, 0.97)], post-illness new diagnosis of significant neurologic injury [0.32 (0.13, 0.82)], and subsequent occurrence of NEC/sepsis among the survivors [0.34, (0.18, 0.65)]. CONCLUSION: NE may be more effective than DA for management of sepsis-related hypotension among preterm infants. These data provide a rationale for prospective evaluation of these commonly used agents. WHAT IS KNOWN: •Dopamine is the commonest vasoactive agent used to support blood pressure among preterm infants. •For adult patients, norepinephrine is recommended as the preferred therapy over dopamine for septic shock. WHAT IS NEW: •This is the first study examining the relative clinical effectiveness of dopamine and norepinephrine as first-line pharmacotherapy for sepsis-related hypotension among preterm infants. •Norepinephrine use may be associated with lower mortality and morbidity than dopamine in preterm infants with sepsis.

Interventions for patent ductus arteriosus (PDA) in preterm infants: an overview of Cochrane Systematic Reviews.

BACKGROUND: Patent ductus arteriosus (PDA) is associated with significant morbidity and mortality in preterm infants. Several non-pharmacological, pharmacological, and surgical approaches have been explored to prevent or treat a PDA. OBJECTIVES: To summarise Cochrane Neonatal evidence on interventions (pharmacological or surgical) for the prevention of PDA and related complications, and interventions for the management of asymptomatic and symptomatic PDA in preterm infants. METHODS: We searched the Cochrane Database of Systematic Reviews on 20 October 2022 for ongoing and published Cochrane Reviews on the prevention and treatment of PDA in preterm (< 37 weeks' gestation) or low birthweight (< 2500 g) infants. We included all published Cochrane Reviews assessing the following categories of interventions: pharmacological therapy using prostaglandin inhibitor drugs (indomethacin, ibuprofen, and acetaminophen), adjunctive pharmacological interventions, invasive PDA closure procedures, and non-pharmacological interventions. Two overview authors independently checked the eligibility of the reviews retrieved by the search, and extracted data from the included reviews using a predefined data extraction form. Any disagreements were resolved by discussion with a third overview author. Two overview authors independently assessed the methodological quality of the included reviews using the AMSTAR 2 (A MeaSurement Tool to Assess systematic Reviews) tool. We reported the GRADE certainty of evidence as assessed by the respective review authors using summary of findings tables. MAIN RESULTS: We included 16 Cochrane Reviews, corresponding to 138 randomised clinical trials (RCT) and 11,856 preterm infants, on the prevention and treatment of PDA in preterm infants. One of the 16 reviews had no included studies, and therefore, did not contribute to the results. Six reviews reported on prophylactic interventions for the prevention of PDA and included pharmacological prophylaxis with prostaglandin inhibitor drugs, prophylactic surgical PDA ligation, and non-pharmacologic interventions (chest shielding during phototherapy and restriction of fluid intake); one review reported on the use of indomethacin for the management of asymptomatic PDA; nine reviews reported on interventions for the management of symptomatic PDA, and included pharmacotherapy with prostaglandin inhibitor drugs in various routes and dosages, surgical PDA ligation, and adjunct therapies (use of furosemide and dopamine in conjunction with indomethacin). The quality of reviews varied. Two reviews were assessed to be high quality, seven reviews were of moderate quality, five of low quality, while two reviews were deemed to be of critically low quality. For prevention of PDA, prophylactic indomethacin reduces severe intraventricular haemorrhage (IVH; relative risk (RR) 0.66, 95% confidence interval (CI) 0.53 to 0.82; 14 RCTs, 2588 infants), and the need for invasive PDA closure (RR 0.51, 95% CI 0.37 to 0.71; 8 RCTs, 1791 infants), but it does not appear to affect the composite outcome of death or moderate/severe neurodevelopmental disability (RR 1.02, 95% CI 0.90 to 1.15; 3 RCTs, 1491 infants). Prophylactic ibuprofen probably marginally reduces severe IVH (RR 0.67, 95% CI 0.45 to 1.00; 7 RCTs, 925 infants; moderate-certainty evidence), and the need for invasive PDA closure (RR 0.46, 95% CI 0.22 to 0.96; 7 RCTs, 925 infants; moderate-certainty evidence). The evidence is very uncertain on the effect of prophylactic acetaminophen on severe IVH (RR 1.09, 95% CI 0.07 to 16.39; 1 RCT, 48 infants). Necrotising enterocolitis (NEC) was lower with both prophylactic surgical ligation (RR 0.25, 95% CI 0.08 to 0.83; 1 RCT, 84 infants), and fluid restriction (RR 0.43, 95% CI 0.21 to 0.87; 4 RCTs, 526 infants). For treatment of asymptomatic PDA, indomethacin appears to reduce the development of symptomatic PDA post-treatment (RR 0.36, 95% CI 0.19 to 0.68; 3 RCTs, 97 infants; quality of source review: critically low). For treatment of symptomatic PDA, all available prostaglandin inhibitor drugs appear to be more effective in closing a PDA than placebo or no treatment (indomethacin: RR 0.30, 95% CI 0.23 to 0.38; 10 RCTs, 654 infants; high-certainty evidence; ibuprofen: RR 0.62, 95% CI 0.44 to 0.86; 2 RCTs, 206 infants; moderate-certainty evidence; early administration of acetaminophen: RR 0.35, 95% CI 0.23 to 0.53; 2 RCTs, 127 infants; low-certainty evidence). Oral ibuprofen appears to be more effective in PDA closure than intravenous (IV) ibuprofen (RR 0.38, 95% CI 0.26 to 0.56; 5 RCTs, 406 infants; moderate-certainty evidence). High-dose ibuprofen appears to be more effective in PDA closure than standard-dose ibuprofen (RR 0.37, 95% CI 0.22 to 0.61; 3 RCTs, 190 infants; moderate-certainty evidence). With respect to adverse outcomes, compared to indomethacin administration, NEC appears to be lower with ibuprofen (any route; RR 0.68, 95% CI 0.49 to 0.94; 18 RCTs, 1292 infants; moderate-certainty evidence), oral ibuprofen (RR 0.41, 95% CI 0.23 to 0.73; 7 RCTs, 249 infants; low-certainty evidence), and with acetaminophen (RR 0.42, 95% CI 0.19 to 0.96; 4 RCTs, 384 infants; low-certainty evidence). However, NEC appears to be increased with a prolonged course of indomethacin versus a shorter course (RR 1.87, 95% CI 1.07 to 3.27; 4 RCTs, 310 infants). AUTHORS' CONCLUSIONS: This overview summarised the evidence from 16 Cochrane Reviews of RCTs regarding the effects of interventions for the prevention and treatment of PDA in preterm infants. Prophylactic indomethacin reduces severe IVH, but does not appear to affect the composite outcome of death or moderate/severe neurodevelopmental disability. Prophylactic ibuprofen probably marginally reduces severe IVH (moderate-certainty evidence), while the evidence is very uncertain on the effect of prophylactic acetaminophen on severe IVH. All available prostaglandin inhibitor drugs appear to be effective in symptomatic PDA closure compared to no treatment (high-certainty evidence for indomethacin; moderate-certainty evidence for ibuprofen; low-certainty evidence for early administration of acetaminophen). Oral ibuprofen appears to be more effective in PDA closure than IV ibuprofen (moderate-certainty evidence). High dose ibuprofen appears to be more effective in PDA closure than standard-dose ibuprofen (moderate-certainty evidence). There are currently two ongoing reviews, one on fluid restriction for symptomatic PDA, and the other on invasive management of PDA in preterm 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: · Many preterm infants encounter the clinical consequences of a hemodynamically significant PDA.. · The merits and optimal timing of PDA ligation remains an area of controversy amongst neonatologists.. · Cyclooxygenase inhibitors are associated with adverse events or are often contraindicated..

Clinical burden associated with therapies for cardio-pulmonary critical decompensation in preterm neonates across Canadian neonatal intensive care units.

The aim of this retrospective cohort study was to study the clinical burden associated with cardio-pulmonary critical decompensations (CPCDs) in preterm neonates and factors associated with mortality. Through the Canadian Neonatal Network (30 tertiary NICUs, 2010-2017), we identified infants < 32-week gestational age with CPCDs, defined by "significant exposure" to cardiotropes and/or inhaled nitric oxide (iNO): (1) either therapy for ≥ 3 consecutive days, (2) both for ≥ 2 consecutive days, or (3) any exposure within 2 days of death. Early CPCDs (≤ 3 days of age) and late CPCDs (> 3 days) were examined separately. Outcomes included CPCD-incidence, mortality, and inter-site variability using standardized ratios (observed/adjusted expected rate) and network funnel plots. Mixed-effects analysis was used to quantify unit-level variability in mortality. Overall, 10% of admissions experienced CPCDs (n = 2915). Late CPCDs decreased by ~ 5%/year, while early CPCDs were unchanged during the study period. Incidence and CPCD-associated mortality varied between sites, for both early (0.6-7.5% and 0-100%, respectively) and late CPCDs (2.5-15% and 14-83%, respectively), all p < 0.01. Units' late-CPCD incidence and mortality demonstrated an inverse relationship (slope = -2.5, p < 0.01). Mixed-effects analysis demonstrated clustering effect, with 6.4% and 8.6% of variability in mortality after early and late CPCDs respectively being site-related, unexplained by available patient-level characteristics or unit volume. Mortality was higher with combined exposure than with only-cardiotropes or only-iNO (41.3%, 24.8%, 21.5%, respectively; p < 0.01). CONCLUSIONS: Clustering effects exist in CPCD-associated mortality among Canadian NICUs, with higher incidence units showing lower mortality. These data may aid network-level benchmarking, patient-level risk stratification, parental counseling, and further research and quality improvement work. WHAT IS KNOWN: • Preterm neonates remain at high risk of acute and chronic complications; the most critically unwell require therapies such as cardiotropic drugs and inhaled nitric oxide. • Infants requiring these therapies are known to be at high risk for adverse neonatal outcomes and for mortality. WHAT IS NEW: • This study helps illuminate the national burden of acute cardio-pulmonary critical decompensation (CPCD), defined as the need for cardiotropic drugs or inhaled nitric oxide, and highlights the high risk of morbidity and mortality associated with this disease state. • Significant nationwide variability exists in both CPCD incidence and associated mortality; a clustering effect was observed with higher incidence sites showing lower CPCD-associated mortality.

Physiology of Low Blood Pressure During the First Day After Birth Among Extremely Preterm Neonates.

OBJECTIVE: To investigate the circulatory physiology of hypotension during the first day after birth among stable extremely preterm neonates. STUDY DESIGN: Case-control study of neonates born at ≤276/7 weeks gestational age with hypotension, defined as mean blood pressure in mmHg less than gestational age in weeks for at least 1 hour during the first 24 hours after birth, who underwent comprehensive echocardiography assessment before commencement of cardiovascular drugs. Neonates with hypotension (n = 14) were matched by gestational age and intensity of respiratory support with normotensive neonates (n = 27) who underwent serial echocardiography during the first day after birth, and relatively contemporaneous echocardiography assessments were used for comparison. RESULTS: Neonates with hypotension had a higher frequency of patent ductus arteriosus ≥1.5 mm (71% vs 15%; P < .001) and ductal size (median diameter, 1.6 mm [IQR, 1.4-2.1] vs 1.0 mm [IQR, 0-1.3]; P = .002), higher echocardiography indices of left ventricular systolic function (mean shortening fraction, 34 ± 7% vs 26 ± 4%; P < .001; mean longitudinal strain, -16 ± 5% vs -14 ± 3%; P = .04; and mean velocity of circumferential fiber shortening, 1.24 ± 0.35 circ/s vs 1.01 ± 0.28 circ/s; P = .03), lower estimates of left ventricular afterload (mean end-systolic wall stress, 20 ± 7 g/cm2 vs 30 ± 9 g/cm2; P < .001 and mean arterial elastance, 43 ± 19 mmHg/mL vs 60 ± 22 mmHg/mL; P = .01), without significant difference in stress-velocity index z-score (-0.42 ± 1.60 vs -0.88 ± 1.30; P = .33). Neonates with hypotension had higher rates of any degree of intraventricular hemorrhage (71% vs 22%; P = .006). CONCLUSIONS: Low blood pressure in otherwise well extremely low gestational age neonates was associated with low systemic afterload and larger patent ductus arteriosus, but not left ventricular dysfunction.

Percutaneous Closure of Patent Ductus Arteriosus in Infants 1.5 kg or Less: A Meta-Analysis.

OBJECTIVE: To investigate technical success and safety of percutaneous patent ductus arteriosus closure in infants ≤1.5 kg. STUDY DESIGN: A systematic review and meta-analysis was performed. Data sources included Scopus, Web of Science, Embase, CINAHL, Cochrane, and PubMed from inception to April 2020. Publications were included if they had a clear definition of the intervention as percutaneous patent ductus arteriosus closure in infants ≤1.5 kg. Data extraction was independently performed by multiple observers. Primary outcome was technical success and secondary outcomes were adverse events (AEs). Subgroup analysis was performed in infants ≤6.0 kg. Data were pooled by using a random-effects model. RESULTS: We included 28 studies, including 373 infants ≤1.5 kg and 69 studies enrolling 1794 infants ≤6.0 kg. In patients ≤1.5 kg, technical success was 96% (95% CI, 93%-98%; P = .16; I2 = 23%). The overall incidence of AE was 27% (95% CI, 17%-38%; P < .001; I2 = 70%) and major AEs was 8% (95% CI, 5%-10%; P = .63; I2 = 0%). There were 5 deaths related to the procedure (2%; 95% CI, 1%-4%; P = .99; I2 = 0%); 4 of these deaths occurred in infants <0.8 kg. The probability of technical failure was inversely related to age at the time of the procedure (OR, 0.9; 95% CI, 0.830-0.974; P = .009). Weight at intervention has decreased over time and procedural success has increased. CONCLUSIONS: Percutaneous patent ductus arteriosus closure is feasible in infants ≤1.5 kg with few major AEs. The procedural success rate is high, despite performing the intervention in smaller patients. PROSPERO REGISTRATION: CRD42020145230.

Bloodstream Infections in Preterm Neonates and Mortality-Associated Risk Factors.

OBJECTIVE: To investigate the association of early (±4 hours after onset of bloodstream infection) clinical and laboratory variables with episode-related mortality (<7 days). STUDY DESIGN: This 2-site retrospective study included 142 neonates born at <35 weeks of gestational age with positive blood/cerebrospinal fluid (CSF) culture at >72 hours of age from organisms other than coagulase-negative Staphylococcus. Early variables were compared between those with bloodstream infection-related mortality and survivors. Multivariable analysis was conducted for the primary outcome, and the area under the curve (AUC) was estimated for relevant variables. RESULTS: The neonates who died were of lower gestational age at disease onset. After adjusting for relevant variables, lowest mean blood pressure (MBP) (aOR, 0.10; 95% CI, 1.02-1.19) and highest base deficit (aOR, 1.18; 95% CI, 1.06-1.32) were independently associated with mortality. The AUC was 0.87 (95% CI, 0.78-0.96) for base deficit, increasing to 0.91 (95% CI, 0.83-0.99) with the addition of MBP. CONCLUSION: Low MBP and high base deficit within ±4 hours of bloodstream infection onset identify preterm neonates at risk of mortality.

Predictors of Early Extubation after Patent Ductus Arteriosus Ligation among Infants Born Extremely Preterm Dependent on Mechanical Ventilation.

We conducted a retrospective study of 166 ventilator-dependent neonates born extremely preterm in whom patent ductus arteriosus was surgically ligated and evaluated the association of preoperative characteristics and time-to-successful postoperative extubation. Larger patent ductus arteriosus diameter ([>2.5 mm], adjusted hazard ratio 0.51, 95% CI 0.36-0.72) and left-ventricular dilatation (z score ≥2, adjusted hazard ratio 0.61, 95% CI 0.42-0.87) were associated with earlier extubation.

Accuracy and reliability of qualitative echocardiography assessment of right ventricular size and function in neonates.

BACKGROUND: Subjective assessment of right ventricular (RV) function by neonatal echocardiography lacks validation. Incorrect diagnostic assignment in patients with suspected pulmonary hypertension (PH) may lead to unnecessary treatment or missed treatment opportunities. METHODS: Six evaluators (experts [n = 3], novice [n = 3]) were asked to independently rate RV characteristics (global function, dilation, and septal flattening) based on standardized echocardiography images. We randomly selected 60 infants, ≥35 weeks gestation at birth, of whom 30 were clinically unwell with acute pulmonary hypertension (aPH) and 30 were healthy controls. aPH was defined by echocardiography presence of right-left shunting across transitional shunts or elevated right ventricular systolic pressure as estimated by the magnitude of the regurgitant jet across the tricuspid valve with impaired oxygenation. Inter-rater comparative evaluation within groups and between groups was performed using Kappa statistics. RESULTS: Global agreement between evaluators for subjective assessment of RV function (0.3 [0.03], P < 0.001), size (0.14 [0.02], P < 0.001), and septal flattening (0.2 [0.02], P < 0.001) was uniformly poor. Agreement in RV function assessment was marginally better for both expert (0.32 [0.08], P < 0.001 vs 0.13 [0.081], and P < 0.001) and novice (0.4 [0.08], P < 0.001 vs 0.06 [0.07], and P < 0.001) evaluators. Overall, the diagnosis of aPH vs control was misclassified in 18% of cases. CONCLUSION: This study demonstrated significant variability in qualitative assessment of RV size and function by trained evaluators, regardless of level of expertise attained. The reliability of objective measures of RV hemodynamics requires prospective evaluation.

Clinical and echocardiography predictors of response to inhaled nitric oxide in hypoxic preterm neonates.

AIM: To evaluate the clinical and echocardiography modulators of treatment response in hypoxemic preterm infants exposed to inhaled nitric oxide (iNO). METHODS: In this multicentre retrospective study, clinical parameters, including oxygenation, ventilation and haemodynamics, were collected for preterm infants <36 weeks gestation before and 2 h after initiation of iNO for acute hypoxemia. Comprehensive echocardiography, performed near the time iNO initiation, was analysed by experts blind to the clinical course. Multiple logistic regression analysis was used to identify factors associated with iNO response as defined by a reduction in the fraction of inspired oxygen by >0.20. RESULTS: A total of 213 infants met eligibility criteria, of which 73 had echocardiography data available and formed the study cohort. Response to iNO was demonstrated in 56% of patients. Younger post-natal age (odds ratio (OR) 0.94; 95% confidence interval (CI) 0.89, 0.99) and the presence of pulmonary hypertension (PH) (OR 4.47; 95% CI 1.23-11.9) were independently predictive of iNO response regardless of gestational age. Among neonates <72 h old with documented PH, iNO response was seen in 82%. The onset of a new diagnosis of severe (grade III/IV) intraventricular haemorrhage (IVH) after iNO treatment was seen in 6 of 40 patients <28 weeks' gestational age, with a greater frequency in responders (32 vs. 0%, P = 0.02). CONCLUSIONS: Positive response to iNO is greatest in the first 3 days of life and in patients with echo-confirmed PH, independent of gestational age. The association between critical illness, iNO administration and IVH in extremely premature infants may merit prospective delineation.

Outcomes of Surgical Ligation after Unsuccessful Pharmacotherapy for Patent Ductus Arteriosus in Neonates Born Extremely Preterm.

A retrospective cohort study of neonates born extremely preterm with persistent patent ductus arteriosus after unsuccessful pharmacologic closure compared outcomes between 166 surgically ligated and 142 nonligated neonates. After adjustment for confounders, ligation was not associated with the composite outcome of death or neurodevelopmental impairment, neurodevelopmental impairment alone, chronic lung disease, or retinopathy of prematurity among survivors.

An innovative on-call system for paediatric residency programs: The alternate night float.

BACKGROUND: Night-float systems, in which residents work consecutive nights, have been increasingly adopted in paediatric programs, but may be detrimental to residents' sleep and mood. OBJECTIVE: To describe the self-reported impact of a novel system consisting of two consecutive weeks of 16 h overnight shifts every second day that was piloted at the Children's Hospital of Eastern Ontario (Ottawa, Ontario). METHODS: A survey of 28 senior paediatric residents examined their experience with the alternate night-float system in three domains (patient care, resident professional development and well-being) and their comparison of the system with the traditional overnight on-call system. RESULTS: Twenty-six of 28 residents responded. Nearly all (96%) felt familiar with important details of inpatients and that handover was effective (92%). Results were mixed for professional development, with concerns about the quality of supervisors' feedback and perceived difficulty in attending daytime teaching. All residents believed that the night-float system provided a better learning experience compared with the traditional system. Less than 35% considered fatigue to be a notable problem, although 20% increased use of sleep aids or stimulants beyond their typical use. Ninety-six percent believed their workload was appropriate. All residents felt equally or less fatigued under the night-float system compared with the traditional system. Ninety-six percent recommended that the night-float model continue as the on-call system. CONCLUSIONS: This novel night-float system is an alternative method of providing paediatric inpatient night coverage because it meets duty hour regulations and has strong resident approval. Studies to examine its impact on residents and patient care in comparison with other systems are warranted.

HISTORIQUE: Les systèmes de garde de nuit, dans le cadre desquels les résidents travaillent plusieurs nuits consécutives, sont de plus en plus fréquents dans les programmes de pédiatrie, mais ils peuvent nuire au sommeil et à l'humeur des résidents. OBJECTIF: Décrire les répercussions autodéclarées d'un nouveau système constitué de deux semaines consécutives de quarts de nuit de 16 heures tous les deux jours, piloté à Ottawa, au Centre hospitalier pour enfants de l'est de l'Ontario. MÉTHODOLOGIE: Dans un sondage auprès de 28 résidents seniors en pédiatrie, les chercheurs ont examiné l'expérience de ces résidents au sein du système de garde de nuit tous les deux jours (soins aux patients, bien-être des résidents et perfectionnement professionnel) et les comparaisons que ces résidents ont faites avec le système de garde de nuit habituel. RÉSULTATS: Vingt-six des 28 résidents ont répondu. Presque la totalité (96 %) connaissait l'information importante sur les patients hospitalisés et trouvait le transfert des soins efficace (92 %). Les résultats étaient mitigés à l'égard du perfectionnement professionnel, car les résidents se préoccupaient de la qualité de la rétroaction des superviseurs et trouvaient difficile d'assister à l'enseignement pendant la journée. Tous les résidents trouvaient que le système de garde de nuit assurait une meilleure expérience d'apprentissage que le système habituel. Moins de 35 % considéraient la fatigue comme un problème notable, même si 20 % utilisaient plus d'aides au sommeil ou de stimulants qu'à l'habitude. De plus, 96 % trouvaient leur charge de travail adéquate. Tous les résidents se sentaient aussi fatigués ou moins fatigués dans le système de garde de nuit que dans le système habituel. Enfin, 96 % recommandaient d'adopter le modèle de garde de nuit comme système de garde. CONCLUSIONS: Ce nouveau système de garde de nuit est une autre méthode pour assurer les services nocturnes auprès des enfants hospitalisés. Il respecte la réglementation sur les heures de garde et est fortement approuvé par les résidents. Des études s'imposent pour en examiner les effets sur les résidents et les soins aux patients par rapport aux autres systèmes.

Combination pharmacotherapy for patent ductus arteriosus: Rationale and evidence.

While cyclooxygenase inhibitors have been the most common medications used to facilitate earlier closure of patent ductus arteriosus in preterm infants, adverse effects and low efficacy in extremely low gestational age neonates (ELGANs) have highlighted a need for alternative options. Combination therapy with acetaminophen and ibuprofen is a novel strategy for PDA treatment in ELGANs, as it may facilitate higher ductal closure rates via additive action on two separate pathways inhibiting prostaglandin production. Initial small observational studies and pilot randomized clinical trials indicate potentially higher efficacy of the combination regime to induce ductal closure in comparison to treatment with ibuprofen alone. In this review, we examine the potential clinical impact of treatment failure in ELGANs with significant PDA, highlight the biological rationale in support of studying combination therapy, and review the randomized and non-randomized studies to date. With the rising number of ELGANs receiving neonatal intensive care, who are vulnerable to PDA-related morbidities, there is an urgent need for adequately powered clinical trials to systematically investigate the efficacy and safety of combination therapy for PDA treatment.

Vasopressin for refractory persistent pulmonary hypertension of the newborn in preterm neonates - a case series.

OBJECTIVE: To describe the clinical outcomes following treatment with vasopressin for a sub-cohort of critically ill preterm neonates who have refractory persistent pulmonary hypertension of the newborn (PPHN). DESIGN: Case series. SETTING: Tertiary neonatal intensive care unit, Toronto, Canada. POPULATION: Neonates born <37 weeks gestational age (GA) who received vasopressin for refractory PPHN (lack of response to inhaled nitric oxide) over a 4-year period. MEASUREMENTS: Changes in physiological indices of cardio-pulmonary stability during vasopressin therapy were analyzed using one-way repeated measures ANOVA, compared to pretreatment values. Data regarding survival to discharge and neurodevelopmental outcomes at 18-24 months were described. MAIN RESULTS: Thirteen neonates with a mean GA of 31.4 ± 3.3 weeks were included. Vasopressin was initiated at 28.5 ± 4.5 h of age. Overall, oxygenation and hemodynamic variables improved significantly following vasopressin therapy (p < .05 at 24 h vs. pretreatment). Oxygenation failure resolved in 8 cases, of which 7 patients survived (6 without disability). Among the 5 cases where oxygenation failure persisted despite vasopressin, 4 died while one survived with disability. CONCLUSIONS: Vasopressin offers promise as a therapy for preterm neonates with refractory PPHN and hemodynamic instability, but prospective investigation is needed.

Care of the critically ill neonate with hypoxemic respiratory failure and acute pulmonary hypertension: framework for practice based on consensus opinion of neonatal hemodynamics working group.

Circulatory transition after birth presents a critical period whereby the pulmonary vascular bed and right ventricle must adapt to rapidly changing loading conditions. Failure of postnatal transition may present as hypoxemic respiratory failure, with disordered pulmonary and systemic blood flow. In this review, we present the biological and clinical contributors to pathophysiology and present a management framework.

Patent Ductus Arteriosus: A Contemporary Perspective for the Pediatric and Adult Cardiac Care Provider.

The burden of patent ductus arteriosus (PDA) continues to be significant. In view of marked differences in preterm infants versus more mature, term counterparts (viewed on a continuum with adolescent and adult patients), mechanisms regulating ductal patency, genetic contributions, clinical consequences, and diagnostic and treatment thresholds are discussed separately, when appropriate. Among both preterm infants and older children and adults, a range of hemodynamic profiles highlighting the markedly variable consequences of the PDA are provided. In most contemporary settings, transcatheter closure is preferable over surgical ligation, but data on longer-term outcomes, particularly among preterm infants, are lacking. The present review provides recommendations to identify gaps in PDA diagnosis, management, and treatment on which subsequent research can be developed. Ultimately, the combination of refined diagnostic thresholds and expanded treatment options provides the best opportunities to address the burden of PDA. Although fundamental gaps remain unanswered, the present review provides pediatric and adult cardiac care providers with a contemporary framework in PDA care to support the practice of evidence-based medicine.

Trends in patent ductus arteriosus ligation in neonates and changes in outcomes: A 10-year multicenter experience.

RATIONALE: The management of neonates with patent ductus arteriosus (PDA) has changed over time. METHODS: We conducted a single-city, retrospective review of neonates who underwent PDA ligation over a 10-year time period and compared infants from the first 5 years to the second 5 years to evaluate how clinical characteristics changed over this time. RESULTS: Infants from the second 5-year epoch were older at time of ligation (38 vs. 30 days), had a higher ligation weight (1432 vs. 1121 g) and a lower incidence of postligation cardiac syndrome (1.9% vs. 11.5%). No differences in mortality, length of hospital-stay or major morbidities were seen. Compared to neonates who underwent PDA ligation at ≤28 days of life, those with a ligation age >28 days had a higher ligation weight (1421 vs. 1039 g), a higher proportion of COX inhibitor use (92.5% vs. 83.8%), and a higher incidence of moderate-severe bronchopulmonary dysplasia (BPD) (60.4% vs. 44.4%). Only 10.7% (25/233) patients were evaluated by laryngoscopy, in which the incidence of vocal cord paralysis (VCP) was 36.0%; 2 patients were clinically diagnosed with VCP for a total 4.7% incidence of VCP (11/233). CONCLUSIONS: Over the 10 years examined, neonates underwent PDA ligation at an older age in the second 5-year time period; this change was not associated with a change in the incidence of major morbidities. Ligation age >28 days was associated with an increase incidence of moderate-severe BPD. The overall incidence of documented VCP post-PDA ligation was relatively low but was seen in over 1/3 who were evaluated by laryngoscopy.