Oral versus intravenous paracetamol for patent ductus arteriosus closure in preterm infants.

BACKGROUND: To examine whether oral administration of paracetamol as a first-line agent had a greater effect on the closure of a patent ductus arteriosus than the intravenous route. METHODS: We performed a retrospective study of preterm infants (<37 weeks of gestation) between 2012 and 2020 treated with oral or intravenous paracetamol as the first line for patent ductus arteriosus (PDA) constriction and compared rates of ductal closure, course duration, cumulative dose, PDA characteristics, and serum levels. RESULTS: Over the study period, 80 preterm infants received paracetamol, of which 50 received paracetamol as first-line treatment to augment constriction of the PDA. Closure rate was higher in the oral group (n = 15/19, 79%) compared to the intravenous group (n = 8/20, 40%, p < 0.01), and remained significant after adjusting for gestational age, length of treatment, and postnatal age (OR 0.14, 95% CI 0.03-0.67, p = 0.014, RR 0.51, 95% CI 0.28-0.91). Eleven preterm infants received a combination of both oral and intravenous paracetamol with a closure rate of 45% (n = 5). CONCLUSIONS: Oral administration of paracetamol as a first-line agent is more efficacious to constrict the PDA than the intravenous route, irrespective of gestational age or course duration. IMPACT: Our retrospective study comparing the use of oral versus intravenous paracetamol as the first line for patent ductus arteriosus (PDA) constriction in preterm infants demonstrates that oral administration of paracetamol is more efficacious to constrict the PDA than the intravenous route, irrespective of gestational age or course duration. To our knowledge, this is the first published study (prospective or retrospective) to compare the efficacy of oral versus intravenous paracetamol as a first-line treatment for PDA closure in preterm infants. Our finding may improve the rate of PDA closure when paracetamol is used as a first-line agent.

Using heated humidified high-flow nasal cannulas for premature infants may result in an underestimated amount of water reaching the airways.

AIM: Condensation often occurs when providing humidified respiratory support. We examined conditions conducive to excess water formation in heated humified high-flow nasal cannula (HHHFNC). METHODS: An HHHFNC device, at 35 or 37°C, was attached with a nasal cannula to a reservoir and tested in five ambient conditions and flows. For Group A, tubing and collection bottle remained at room temperature (23°C). Group B, tubing and reservoir remained inside an incubator (31°C). Group C, tubing and reservoir remained at 33°C. In Group D, the HHHFNC was set to 35°C, the reservoir remained at 33°C, and the nasal cannula and tubing remained at 23°C. Group E, same as D, with HHHFNC at 37°C. RESULTS: The largest amounts of collected water were in groups A and E. Both had highest temperature differences. Median (range) was 4.9°C (4.1-6.9) and 4.0°C, collecting 38.4 (26.4-50.4) and 26.4 (19.2-50.4) ml/24 h, respectively. Smallest amounts of water were seen with lower temperature differences as in groups B, C, and D with 2.7 (1.9-4.7), 1.6 (1.2-2.1), and 2.0°C with 8.4 (0.0-33.6), 2.4 (0.0-14.4), and 9.6 (4.8-16.8) ml/24 h, respectively. CONCLUSION: HHHFNC devices may produce clinically significant amounts of water reaching the upper airways. This may be prevented with appropriate device set-up.

[FUNCTIONAL ECHO IN PRETERM INFANTS - PAST, PRESENT AND FUTURE].

INTRODUCTION: The use of point of care ultrasound to assess cardiovascular function performed by a neonatologist who is not a cardiologist, is gaining interest in the neonatal intensive care unit (NICU). Clinical signs such as heart rate, blood pressure and capillary refill time provide limited insight into the adequacy of systemic blood flow and organ perfusion. Functional echocardiography (echo) enables real time evaluation of cardiac performance, identifying the nature of cardiovascular compromise, guiding therapeutic decisions and monitoring response to treatment. Application of functional echo in the NICU includes assessment of patent ductus arteriosus (PDA), pulmonary hypertension, shock and placement of umbilical catheters. There is evidence implicating that functional echo alters neonatal treatment and may improve outcome. Functional echo does not aim to replace the detailed structural assessments provided by consultative services of pediatric cardiologists. Close collaboration with pediatric cardiology is essential. In the past two years there is an increasing awareness for using functional echocardiography by neonatologists in Israel. Three conferences and an educational workshop were held in Israel with world renowned lecturers. Protocols defining how the exam should be performed were prepared, and agreement was reached with pediatric cardiologists on how to implement the use of functional echo by neonatologists, with the intention to create a distinct group of neonatologists with knowledge and skills in functional echo and a profound understanding of cardiac and respiratory physiology and hemodynamics.

Melatonin Stability in Human Milk.

Introduction: Melatonin is an antioxidant, a circadian pacemaker, and an immune system stimulator. Studies have demonstrated beneficial effects of melatonin on various conditions in neonates. Melatonin is secreted in breast milk in circadian rhythm, but its half-life and stability in this medium and in real-life conditions of freezing and defrosting is unknown. The objective of this feasibility study was to evaluate stability of melatonin in breast milk after freezing and defrosting. Methods and Results: Breast milk samples of nocturnal milk and daytime milk were collected from 13 healthy breastfeeding mothers and were immediately frozen. Samples were defrosted in room temperature and were sampled for melatonin immediately and every hour for 4 hours and at 24 hours after defrosting. Melatonin levels were measured with Melatonin direct Saliva ELISA kit (IBL International).There was no statistically significant difference between levels at the different time points (p = 0.696). Melatonin levels in daytime milk were significantly lower than night-time levels (p = 0.028). Conclusion: Melatonin is stable in human milk for at least 4 hours after defrosting and even up to 24 hours. Further research of the therapeutic potential of night breast milk high in melatonin is needed.

While waiting for a vaccine: opportunities for optimization of neonatal group B streptococcal (GBS) disease prevention in Israel.

OBJECTIVE: To quantify effects of different strategies for decreasing neonatal early onset GBS sepsis (EOGBS) in Israel. STUDY DESIGN: A risk allocation model for EOGBS among infants ≥ 35w was adapted to Israeli data. Effects of strategies for antepartum (APS) and intrapartum (IPS) screening, and intrapartum (IAP) and/or postpartum antibiotic prophylaxis (PAP) were calculated. RESULTS: Estimated EOGBS attack rates (AR) with APS in 90%, IAP in 90%, may reduce AR to 0.18/1000. A rapid intrapartum test would further decrease AR to 0.16/1000, while reducing IAP from 21.3 to 12.5% of women. For babies with risk factors and GBS+ who do not receive IAP, further risk reduction could be achieved by PAP. CONCLUSION: IAP remains the main intervention to decrease EOGBS. IAP and PAP together may reduce EOGBS present incidence by 40%. Combining rapid intrapartum screening with selective IAP and selective PAP for remaining gaps, would be the most efficient strategy.

Student-centered tutoring as a model for patient-centeredness and empathy.

BACKGROUND: Curriculum planners and medical teachers attempt to enhance medical students' empathy and patient-centeredness. Despite educational efforts, there is stability in medical students' empathy and patient-centered medicine during the preclinical stage and a decline in both of them throughout the clinical years. Student-tutor relationship plays a key role in students' learning. This study tests the effect of learner-centered tutoring on students' empathy, patient-centeredness, and behavior. PARTICIPANTS AND METHODS: The cohort of 55 students was divided into groups of seven or eight. The experimental group's tutors underwent LC mentoring. Empathy was assessed with the Jefferson Scale of Physician Empathy for Students; PC attitude was assessed with the Patient-Provider Orientation Scale (PPOS). Behavior was assessed by simulations of doctor-patient encounters with 32 students at the end of the third year. Each student participated in three such simulations, during which we analyzed ten aspects of physician-patient communication via Roter interaction analysis system (RIAS)-coded audiotapes. RESULTS: A significant group difference was found for three RIAS categories: building a relationship and patient-centeredness, where the mean percentage of the experimental group was significantly higher than that of the control group, and gathering data, where the mean percentage of the experimental group was significantly lower than that of the control group. A significant correlation was found in the experimental group between empathy and positive talk and between PPOS and three of the RIAS categories: gathering data, psychosocial talk, and patient-centeredness. A significant negative correlation was found in the experimental group between PPOS and two of the RIAS categories: negative talk and doctor-centeredness. Two significant negative correlations were found in the control group: between empathy and patient-centeredness and PPOS and negative talk. CONCLUSION: The LC approach supports two of the RIAS categories, corresponding to clinical empathy and PC care and the link between certain behaviors and the PPOS.

Does Haptoglobin Phenotype Influence Postnatal Morbidity in Preterm Neonates?

BACKGROUND: Haptoglobin (Hp) is an acute phase protein with antioxidant, bacteriostatic, and anti-inflammatory activities. Hp proteins associated with the three major phenotypes differ in their proinflammatory and anti-inflammatory action. Inflammation and oxidative stress are both involved in most pathophysiological processes in premature infants. The objective of this study was to determine whether Hp phenotype influences clinical manifestations and sepsis incidence in the premature infants. OBJECTIVE: Infants born before 35 weeks gestational age were prospectively evaluated for Hp phenotype and clinical events, including sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia, intraventricular hemorrhage, and retinopathy of prematurity. The participants were observed until discharge. METHODS: A total of 122 preterm infants were enrolled in the study. Clinical events were not affected by the Hp phenotype. The expression of Hp protein was extremely low in the study population. More septic episodes were found in infants with a birth weight greater than 1,500 g, although, the difference was not statistically significant. RESULTS: Extremely low expression of Hp may explain the lack of a correlation between Hp phenotype and sepsis in preterm infants. Further research involving a larger neonatal population is required to better understand the role of the Hp phenotype in morbidity of premature infants.

'Becoming a Physician'-medical students get acquainted with disadvantaged populations, and practise sensitive and effective communication.

BACKGROUND: The three-year pre-medical programme 'Becoming a Physician' focuses on different aspects of medical professionalism. Objectives are to increase awareness and sensitivity to disadvantaged populations, and practise sensitive effective communication skills. METHODS: The curriculum includes: (1) Visits to treatment centres for people with special needs, mental illnesses, substance abuse issues, physically or sexually abused, and prisoners. Students tour the facility, hold discussions with residents, and discuss ethical professional interrelations to the medical world. Students then write 'reflective diaries' summarizing their thoughts and emotions. (2) Participation in a communication course that focuses on learning by practising patient-oriented communication. Qualitative data were collected from three sources: reflective diaries, students' course evaluations, and interviews with the students' tutors. RESULTS: Data indicated that the students were very satisfied with the programme. They indicated an increase in awareness of the special needs of diverse populations, and in the sense of efficacy for conducting interviews tailored to patients' needs. Tutors reported a sense of 'personal growth' following their role as mentors. REFLECTIONS: Interactions of medical students with diverse populations, when accompanied by appropriate feedback mechanisms and strengthening of communication skills, can improve awareness and sensitivity to patients' special needs. This could help students become more sensitive and thoughtful physicians.

Bilateral vocal cord paralysis and hypothyroidism as presenting symptoms of Williams-Beuren syndrome: a case report.

Williams-Beuren syndrome is a rare neurodevelopmental disorder caused by deletion of 1.5-1.8Mb genes on chromosome 7q11.23. The syndrome was first described as a triad of supra-valvular aortic stenosis, mental retardation, and distinctive facial features. Our patient was referred due to audible inspiratory stridor when he was seven days old. Following endoscopy he was diagnosed with bilateral vocal cord paralysis and was eventually intubated due to respiratory de-compensation followed by tracheotomy. On further workup he was diagnosed with hypothyroidism. Genetic workup supported the diagnosis of Williams-Beuren syndrome. We report here a case with an unusual clinical presentation.

Real-time detection, classification, and quantification of apneic episodes using miniature surface motion sensors in rats.

BACKGROUND: Real-time detection and classification of apneic episodes remain significant challenges. This study explores the applicability of a novel method of monitoring the respiratory effort and dynamics for rapid detection and classification of apneic episodes. METHODS: Obstructive apnea (OA) and hypopnea/central apnea (CA) were induced in nine tracheostomized rats, by short-lived airway obstruction and administration of succinylcholine, respectively. Esophageal pressure (EP), EtCO2, arterial O2 saturation (SpO2), heart rate, and blood pressure were monitored. Respiratory dynamics were monitored utilizing three miniature motion sensors placed on the chest and epigastrium. Three indices were derived from these sensors: amplitude of the tidal chest wall displacement (TDi), breath time length (BTL), that included inspiration and rapid expiration phases, and amplitude time integral (ATI), the integral of breath amplitude over time. RESULTS: OA induced a progressive 6.42 ± 3.48-fold increase in EP from baseline, which paralleled a 3.04 ± 1.19-fold increase in TDi (P < 0.0012), a 1.39 ± 0.22-fold increase in BTL (P < 0.0002), and a 3.32 ± 1.40-fold rise in the ATI (P < 0.024). During central hypopneic/apneic episodes, each sensor revealed a gradual decrease in TDi, which culminated in absence of breathing attempts. CONCLUSION: Noninvasive monitoring of chest wall dynamics enables detection and classification of central and obstructive apneic episodes, which tightly correlates with the EP.

[Why perform routine brain sonography in late preterm infants?].

We present a case of a late preterm baby with respiratory distress syndrome (RDS), prolonged jaundice and congenital hypothyroidism. The infant developed late lenticulostriate vasculopathy (LSV). LSV was previously described in association with various neurodevelopmental abnormalities and in this case would have been missed by the current US brain screening recommendations for newborns.

Paracetamol effectiveness, safety and blood level monitoring during patent ductus arteriosus closure: a case series.

Paracetamol was reported to be effective for patent ductus arteriosus (PDA) closure. We present a case series of PDA closure by paracetamol in seven premature infants. During the treatment, paracetamol blood levels did not exceed the recommended levels for analgesia and hyperthermia in six tested infants. None of the patients demonstrated significant disturbances of liver function.

[Hypothermia as a treatment for hypoxic ischemic encephalopathy after neonatal asphyxia--update].

Hypoxic-ischemic encephalopathy (HIE) due to neonatal asphyxia is an important cause of irreversible bad neurodevelopmental outcomes in children. Understanding the mechanisms causing the central nervous system cell death enabled the development of new treatment strategies that may decrease the severity of neurological damage. This survey includes data on epidemiology, pathogenesis, clinical features and diagnostic criteria of HIE. We discuss the neuro-protective mechanisms of therapeutic hypothermia and provide data on clinical studies conducted to investigate the impact and safety of this treatment in newborn infants affected by HIE. In addition, other therapeutic options of neuro-protective agents are mentioned.

Transient decrease in PaCO(2) and asymmetric chest wall dynamics in early progressing pneumothorax.

PURPOSE: Diagnosis of pneumothorax (PTX) in newborn infants has been reported as late. To explore diagnostic indices for early detection of progressing PTX, and offer explanations for delayed diagnoses. METHODS: Progressing PTX was created in rabbits (2.3 ± 0.5 kg, n = 7) by injecting 1 ml/min of air into the pleural space. Hemodynamic parameters, tidal volume, EtCO(2), SpO(2), blood gas analyses and chest wall tidal displacements (TDi) on both sides of the chest were recorded. RESULTS: (Mean ± SD): A decrease in SpO(2) below 90 % was detected only after 46.6 ± 11.3 min in six experiments. In contrary to the expected gradual increase of CO(2), there was a prolonged transient decrease of 14.2 ± 4.5 % in EtCO(2) (p < 0.01), and a similar decrease in PaCO(2) (p < 0.025). EtCO(2) returned back to baseline only after 55.2 ± 24.7 min, and continued to rise thereafter. The decrease in CO(2) was a mirror image of the 14.6 ± 5.3 % increase in tidal volume. The analysis of endotracheal flow and pressure dynamics revealed a paradoxical transient increase in the apparent compliance. Significant decrease in mean arterial blood pressure was observed after 46.2 ± 40.1 min. TDi provided the most sensitive and earliest sign of PTX, decreasing on the PTX side after 16.1 ± 7.2 min. The TDi progressively decreased faster and lower on the PTX side, thus enabling detection of asymmetric ventilation. CONCLUSIONS: The counterintuitive transient prolonged decrease in CO(2) without changes in SpO(2) may explain the delay in diagnosis of PTX encountered in the clinical environment. An earlier indication of asymmetrically decreased ventilation on the affected side was achieved by monitoring the TDi.

Early detection of deteriorating ventilation by monitoring bilateral chest wall dynamics in the rabbit.

PURPOSE: Mechanical complications during assisted ventilation can evolve due to worsening lung disease or problems in airway management. These complications affect lung compliance or airway resistance, which in turn affect the chest wall dynamics. The objective of this study was to explore the utility of continuous monitoring of the symmetry and dynamics of chest wall motion in the early detection of complications during mechanical ventilation. METHODS: The local tidal displacement (TDi) values of each side of the chest and epigastrium were measured by three miniature motion sensors in 18 rabbits. The TDi responses to changes in peak inspiratory pressure (n = 7), induction of one-lung intubation (n = 7), and slowly progressing pneumothorax (PTX) (n = 6) were monitored in parallel with conventional respiratory (SpO(2), EtCO(2), pressure and flow) and hemodynamic (HR and BP) indices. PTX was induced by injecting air into the pleural space at a rate of 1 mL/min. RESULTS: A strong correlation (R(2) = 0.99) with a slope close to unity (0.94) was observed between percent change in tidal volume and in TDi. One-lung ventilation was identified by conspicuous asymmetry development between left and right TDis. These indices provided significantly early detection of uneven ventilation during slowly developing PTX (within 12.9 ± 6.6 min of onset, p = 0.02) almost 1 h before the SpO(2) dropped (77.3 ± 27.4 min, p = 0.02). Decreases in TDi of the affected side paralleled the progression of PTX. CONCLUSIONS: Monitoring the local TDi is a sensitive method for detecting changes in tidal volume and enables early detection of developing asymmetric ventilation.

A new method for continuous monitoring of chest wall movement to characterize hypoxemic episodes during HFOV.

INTRODUCTION: Monitoring ventilated infants is difficult during high-frequency oscillatory ventilation (HFOV). This study tested the possible causes of hypoxemic episodes using a new method for monitoring chest wall movement during HFOV in newborn infants. METHODS: Three miniature motion sensors were attached to both sides of the chest and to the epigastrium to measure the local tidal displacement (TDi) at each site. A >20% change in TDi was defined as deviation from baseline. RESULTS: Eight premature infants (postmenstrual age 30.6 ± 2.6 weeks) were monitored during 10 sessions (32.6 h) that included 21 hypoxemic events. Three types of such events were recognized: decrease in TDi that preceded hypoxemia (n = 11), simultaneous decrease in TDi and SpO2 (n = 6), and decrease in SpO(2) without changes in TDi (n = 4). In the first group, decreases in TDi were detected 22.4 ± 18.7 min before hypoxemia, and were due to airway obstruction by secretions or decline in lung compliance. The second group resulted from apnea or severe abdominal contractions. In the third group, hypoxia appeared following a decrease in FiO2. CONCLUSIONS: Monitoring TDi may enable early recognition of deteriorating ventilation during HFOV that eventually leads to hypoxemia. In about half of cases, hypoxemia is not due to slowly deteriorating ventilation.

Benefits of high frequency oscillatory ventilation for premature infants.

BACKGROUND: High frequency oscillatoryventilation based on optimal lung volume strategy is one of the accepted modes of ventilatory support for respiratory distress syndrome in very low birth weight infants. In 1999 itwas introduced in our unit as the primary ventilation modality for RDS. OBJECTIVES: To evaluate if the shift to HFOV influenced the outcome of ventilated VLBW infants in the neonatal intensive care unit of Carmel Medical Center. METHODS: Data were obtained from the medical charts of VLBW infants born at Carmel Medical Center, and late mortality data from the Israel Ministry of Internal Affairs records. A retrospective analysis and a comparison with a historical control group ventilated by the conventional method were performed. RESULTS: A total of 232 VLBW infants with RDS were mechanically ventilated during the period 1995 to 2003: 120 were ventilated using HFOV during 1999-2003 and 102 infants using CV during 1995-1999. The mean gestational age of survivors was 27.4 +/- 2 weeks in the HFOV group and 28.4 +/- 2 in the conventional ventilation group (P = 0.03). The sub-sample of infants with birth weight < 1000 g ventilated with HFOV showed higher survival rates than the infants in the conventional ventilation group, 53 vs. 25 (64.6% vs. 44.6%) respectively (P < 0.05). A trend for lower incidence of pulmonary interstitial emphysema was observed in the HFOV group. CONCLUSIONS: The introduction of HFOV based on optimal lung volume strategy proved to be an efficient and safe method of ventilation support for VLBW infants in our unit.

Parental and perinatal factors affecting childhood anthropometry of very-low-birth-weight premature infants: a population-based survey.

BACKGROUND: The perinatal-neonatal course of very-low-birth-weight (VLBW) infants might affect their childhood growth. We evaluated the effect of parental anthropometry and perinatal and neonatal morbidity of VLBW neonates on their childhood growth. METHODS: We obtained parental anthropometry, height and weight at age 6-10.5 years of 334 children born as VLBW infants. Parental, perinatal and neonatal data of these children were tested for association with childhood anthropometry. RESULTS: (1) Maternal and paternal weight standard deviation score (SDS) and discharge weight (DW) SDS were associated with childhood weight SDS (R(2)= 0.111, p < 0.00001); (2) Maternal and paternal height SDS, corrected gestational age (GA) at discharge, maternal assisted reproduction and SGA status were associated with childhood height SDS (R(2)= 0.208, p < 0.00001); (3) paternal weight SDS, DW SDS and surfactant therapy were associated with childhood body mass index (BMI) SDS (R(2)= 0.096, p < 0.00001). 31.1% of VLBW infants had DW SDS < -1.88, and are to be considered small for gestational age ('SGA'). One quarter of these infants did not catch up by age 6-10.5 years. CONCLUSION: Childhood anthropometry of VLBW infants depends on parental anthropometry, postnatal respiratory morbidity and growth parameters at birth and at discharge. Almost one-third of VLBW premature infants had growth restriction at discharge from neonatal intensive care unit (NICU), a quarter of whom did not catch up by age 6-10.5 years.

Subpleural microvascular flow velocities and shear rates in normal and septic mechanically ventilated rats.

Changes in pulmonary microhemodynamics are important variables in a large variety of pathological processes. We used in vivo fluorescent videomicroscopy of the subpleural microvasculature in mechanically ventilated rats to directly monitor microvascular flow velocity (FV) and shear rate in pulmonary arterioles, capillaries, and venules in healthy rats and in septic rats 20 h after cecal ligation and puncture (CLP). Observations were made through a small thoracotomy after injection of fluorescent microspheres (D = 1 microm) into the systemic circulation. The FVs were calculated off-line by frame-by-frame measurements of the distance covered by individual microspheres per unit of time. In healthy rats, inspiratory FV were 1322 +/- 142 microm/s in subpleural arterioles and 599 +/- 25 microm/s in capillaries. The highest FV was found in venules (1552 +/- 132 microm/s). The calculated shear rates were 547 +/- 62/s in arterioles and 619 +/- 19/s in capillaries. The highest shear rates were detected in venules (677 +/- 59/s). No significant changes in FV and shear rates were observed throughout the 1-h observation period in any of the microvascular compartments. Pulmonary microvascular FV and shear rates found in sham-operated rats in the CLP experiments were not significantly different from values of healthy rats. The CLP caused a significant increase in leukocyte sequestration in the lungs and a mean of 27% to 34% decrease in FV in all sections of the pulmonary microvasculature (P < 0.001 in capillaries and P < 0.05 in venules). Also, CLP caused a 23% decrease in capillary shear rate that reached only borderline statistical significance (P < 0.06) and a significant 35% decrease in mean shear rate in venules (P < 0.05). Fluorescent videomicroscopy is offered as a stable and reproducible method for in vivo determinations of pulmonary microhemodynamics in clinically relevant models of sepsis.