Cerebral and peripheral regional oxygen saturation during postnatal transition in preterm neonates.

OBJECTIVE: To evaluate peripheral regional oxygen saturation (rpSO2) and cerebral regional oxygen saturation (rcSO2) during the immediate postnatal transition in late preterm infants with and without the need for respiratory support. STUDY DESIGN: This was a prospective observational study using near-infrared spectroscopy to evaluate changes in rpSO2 and rcSO2. These variables were measured during the first 15 minutes of life after elective cesarean delivery. Peripheral oxygen saturation (SpO2) and heart rate were measured continuously by pulse oximetry, and cerebral fractional tissue oxygen extraction (cFTOE) was calculated. Two groups were compared based on their need for respiratory support: a respiratory support group and a normal transition group. Positive-pressure ventilation was delivered with a T-piece resuscitator, and oxygen was adjusted based on SpO2 values. A Florian respiratory function monitor was used to record the ventilation variables. RESULTS: There were 21 infants in the normal transition group and 21 infants in the respiratory support group. Changes in heart rate over time were similar in the 2 groups. SpO2, rcSO2, and rpSO2 values were consistently higher in the normal transition group. In the respiratory support group, cFTOE values remained significantly elevated for a longer period. CONCLUSION: This systematic analysis of rpSO2, rcSO2, and cFTOE in late preterm infants found significantly lower oxygen saturation values in infants who received respiratory support compared with a normal transition group. We hypothesize that the elevated cFTOE values in the respiratory support group represent compensation for lower oxygen delivery.

Fever and pneumonitis induced by enteric-coated mycophenolate sodium in a patient after kidney transplantation.

Here, we report on a patient after kidney transplantation, who developed fever and pneumonitis due to mycophenolic acid (MPA) treatment. Decreasing MPA dosages improved the symptoms, but after rechallenge with higher MPA doses the symptoms recurred. Discontinuation of MPA resulted in a complete resolution of fever within 24 h and a rapid improvement in pneumonitis. In vitro, the patient's polymorphonuclear neutrophils (PMNs) developed increased oxidative burst when incubated with MPA and N-formyl Met-Leu-Phe. We first report on MPA-induced pneumonitis and show that MPA can induce a pro-inflammatory response in kidney-transplanted patients. These pro-inflammatory changes might be due to paradoxical activation of PMNs.

Cardiac movement identified on prehospital echocardiography predicts outcome in cardiac arrest patients.

INTRODUCTION: The prognostic value of emergency echocardiography (EE) in the management of cardiac arrest patients has previously been studied in an in-hospital setting. These studies mainly included patients who underwent cardiopulmonary resuscitation (CPR) by emergency medicine technicians at the scene and who arrived at the emergency department (ED) still in a state of cardiac arrest. In most European countries, cardiac arrest patients are normally treated by physician-staffed emergency medical services (EMS) teams on scene. Transportation to the ED while undergoing CPR is uncommon. OBJECTIVE: To evaluate the ability of EE to predict outcome in cardiac arrest patients when it is performed by ultrasound-inexperienced emergency physicians on scene. METHODS: We performed a prospective, observational study of nonconsecutive, nontrauma, adult cardiac arrest patients who were treated by physician-staffed urban EMS teams on scene. Participating emergency physicians (EPs) received a two-hour course in EE during CPR. After initial procedures were accomplished, EE was performed during a rhythm and pulse check. A single subxiphoid, four-chamber view was required for study enrollment. We defined sonographic evidence of cardiac kinetic activity as any detected motion of the myocardium, ranging from visible ventricular fibrillation to coordinated ventricular contractions. The CPR had to be continued for at least 15 minutes after the initial echocardiography. No clinical decisions were made based on the results of EE. RESULTS: Forty-two patients were enrolled in the study. The heart could be visualized successfully in all patients. Five (11.9%) patients survived to hospital admission. Of the 32 patients who had cardiac standstill on initial EE, only one (3.1%) survived to hospital admission, whereas four out of 10 (40%) patients with cardiac movement on initial EE survived to hospital admission (p = 0.008). Neither asystole on initial electrocardiogram nor peak capnography value, age, bystander CPR, or downtime was a significant predictor of survival. Only cardiac movement was associated with survival, and cardiac standstill at any time during CPR resulted in a positive predictive value of 97.1% for death at the scene. CONCLUSION: Our results support the idea of focused echocardiography as an additional criterion in the evaluation of outcome in CPR patients and demonstrate its feasibility in the prehospital setting.

Cerebral regional oxygen saturation (crSO2): are different sensors comparable?

BACKGROUND: For measurement of cerebral regional oxygen saturation (crSO2) in neonates, one of the frequently used near-infrared spectroscopy devices is the INVOS 5100 with either the neonatal or pediatric sensor. Measurements between adult and pediatric sensors use different algorithms and differ by 10%. There are no published data comparing neonatal and pediatric sensors. OBJECTIVE: Aim of this study was to compare the neonatal sensor with the pediatric sensor of the INVOS 5100 device in a mixed cohort of neonates to recognize possible differences and enable interpretation of data. METHODS: In 40 neonates, crSO2 was measured in identical positions using both the neonatal and the pediatric sensor under identical conditions. Each sensor was reapplied five times to calculate mean values and standard deviations. RESULTS: Cerebral regional oxygen saturation measurements using the neonatal sensor (mean, 76.1 ± 7.9) and crSO2 measurements using the pediatric sensor (mean, 76.4 ± 8.1) were not different. Reproducibility was not significantly different with similar means of standard deviations (neonatal, 3.7 ± 1.6; pediatric, 3.1 ± 1.3). CONCLUSION: In a mixed cohort of neonates, crSO2 measurements were identical when using the INVOS 5100 neonatal sensor and the pediatric sensor. We conclude that studies using the INVOS 5100 neonatal or pediatric sensor are well comparable.

Indications and Limitations of Sirolimus in the Treatment of Vascular Anomalies-Insights From a Retrospective Case Series.

Background: Despite recent developments, the role of sirolimus in the heterogeneous spectrum of vascular anomalies is yet to be defined, in terms of indication, dosage, and therapy duration, recognizing both its potential and limitations. Methods: We retrospectively analyzed 16 children with vascular anomalies treated with sirolimus in two pediatric centers between 2014 and 2020 [male: n = 7, the median age at diagnosis: 4.6 months (range, 0-281.4)]. In addition, repetitive volumetric analyses of the vascular anomalies were performed when possible (11 cases). Results: Ten patients were diagnosed with vascular malformations and 6 with vascular tumors. The mean therapy duration was 27.2 months (range, 3.5-65). The mean sirolimus level was 8.52 ng/ml (range, 5.38-12.88). All patients except one with central conducting lymphatic anomaly responded to sirolimus, with the most noticeable volume reduction in the first 4-6 months. Additional administration of vincristine was needed in five patients with kaposiform hemangioendothelioma and yielded a response, even in cases, refractory to sirolimus monotherapy. As a single agent, sirolimus led to impressive improvement in a patient with another vascular tumor-advanced epithelioid hemangioendothelioma. Complicated vascular malformations required long-term sirolimus therapy. Side effects of sirolimus included mucositis and laboratory abnormalities. No major infectious episodes were recorded. An infant with COVID-19, diagnosed while on sirolimus therapy, presented with a mild course. Conclusion: In the current series, we reported limitations of sirolimus as monotherapy, addressing the need to redefine its indications, and explore combination regimens and multimodal treatment strategies. Tools for objective evaluation of response trends over time could serve as a basis for the establishment of future therapeutic algorithms.

Regional oxygen saturation of the brain during birth transition of term infants: comparison between elective cesarean and vaginal deliveries.

OBJECTIVE: To evaluate differences in regional oxygen saturation of the brains of term infants of vaginal or cesarean deliveries. STUDY DESIGN: Vaginal delivery (n = 63) and elective cesarean delivery infants were prospectively evaluated for the first 10 minutes after delivery. Peripheral arterial oxygen saturation (SpO(2)) and heart rate were measured on the right hand using pulsoximetry with near infrared spectroscopy. Regional oxygen saturation of the brain (rSO(2)brain) was measured. Fractional tissue oxygen extraction was calculated for each minute. RESULTS: From 4 to 8 minutes, SpO(2) values for cesarean delivery infants were significantly lower than for vaginally delivered infants. Heart rate of the cesarean delivery infants was significantly lower throughout the whole observation period. There was no difference between groups in rSO(2)brain. Fractional tissue oxygen extraction only differed at minute 10. CONCLUSIONS: Although SpO(2) and heart rate were significantly lower in cesarean-delivered infants, there were no differences in rSO(2)brain with respect to mode of delivery.

Successful Postnatal Cardiopulmonary Resuscitation Due to Defibrillation.

An asphyxiated term neonate required postnatal resuscitation. After six minutes of cardio-pulmonary resuscitation (CPR) and two doses of epinephrine, spontaneous circulation returned, but was shortly followed by ventricular fibrillation. CPR and administration of magnesium, calcium gluconate, and sodium bicarbonate did not improve the neonate's condition. A counter shock of five Joule was delivered and the cardiac rhythm immediately converted to sinus rhythm. The neonate was transferred to the neonatal intensive care unit and received post-resuscitation care. Due to prolonged QTc and subsequently suspected long-QT syndrome propranolol treatment was initiated. The neonate was discharged home on day 14 without neurological sequelae.

Regional oxygen saturation of the brain and peripheral tissue during birth transition of term infants.

OBJECTIVE: To evaluate regional tissue oxygenation of the brain and preductal and postductal peripheral (muscle) tissue during immediate transition after birth, and to correlate with peripheral preductal and postductal arterial oxygen saturation. STUDY DESIGN: We conducted a prospective observational study. With near-infrared spectroscopy (NIRS), changes in regional oxygen saturation of the brain (rSO2brain), peripheral preductal tissue (rSO2pre), and peripheral postductal tissue (rSO2post) were measured during the first 10 minutes of life in 59 healthy term infants after elective caesarean delivery. Fractional tissue oxygen extraction was calculated for all 3 regions. RESULTS: Mean rSO2brain increased rapidly from 44% (3 minutes) to 76% (7 minutes); thereafter no significant change occurred. Mean rSO2pre and rSO2post increased constantly from minute 3 to minute 10, from 36%(pre)/27%(post) to 66%(pre)/58%(post). Fractional tissue oxygen extraction decreased in all 3 regions during the first minutes of life. Fractional tissue oxygen extraction of the brain did not change significantly after 5 minutes, and preductal and postductal fractional tissue oxygen extraction did not change significantly after 8 minutes. CONCLUSIONS: During transition, the brain had the highest saturation levels, indicating a preference of oxygen delivery to the brain. Fractional tissue oxygen extraction of the brain reached a plateau earlier compared with peripheral tissue.

Safety and efficacy of the endothelin receptor antagonist macitentan in pediatric pulmonary hypertension.

BACKGROUND: Macitentan, a dual endothelin receptor antagonist (ERA), was approved in 2014 for the treatment of adults with idiopathic pulmonary arterial hypertension (PAH). Once-per-day dosing and low potential hepatic toxicity make macitentan an appealing therapeutic option for children with PAH, but reports on its use in pediatric patients are still lacking. METHODS: Prospective observational study of 18 children [10 male; median age: 8.5, minimum (min.): 0.6, maximum (max.): 16.8 years] with pulmonary hypertension (PH). Four of these 18 patients were treatment-naïve and started on a de novo macitentan therapy. The remaining 14/18 children were already on a PH-targeted pharmacotherapy (sildenafil or bosentan as monotherapy or in combination). Nine children who were on bosentan were switched to macitentan. We analyzed the 6-minute walking distance (6MWD), NYHA functional class (FC)/modified ROSS score, invasive hemodynamics, echocardiographic variables and the biomarker N-terminal pro-brain natriuretic peptide (NT-proBNP). RESULTS: The median follow up was 6 months (min.: 0.5, max.: 30). Macitentan treatment was associated with improvement of invasive hemodynamics, e.g., the ratio of mean pulmonary arterial pressure/mean systemic arterial pressure decreased from a median of 62% (min.: 30%, max.: 87%) to 49% (min.: 30%, max.: 69%), P<0.05; pulmonary vascular resistance index (PVRi) decreased from a median of 7.6 (min.: 3.3, max.: 11.5) to 4.8 Wood units × m2 body surface area (min.: 2.5, max.: 10), P<0.05. The tricuspid annular plane systolic excursion (TAPSE) increased from a median of 1.4 (min.: 0.8, max.: 2.8) to 1.9 (min.: 0.8, max.: 2.7) cm, (P<0.05). NT-proBNP values decreased from a median of 272 (min.: 27, max.: 2,010) to 229 (min.: 23, max.: 814) pg/mL under macitentan therapy (P<0.05). The 6MWD and NYHA FC/modified ROSS score did not change significantly. CONCLUSIONS: This is the first prospective study of macitentan pharmacotherapy in infants and children with PH <12 years of age. Except in one patient, macitentan treatment was well tolerated and was associated with improvements in invasive hemodynamics, longitudinal systolic RV function (TAPSE) and serum NT-proBNP values.

Severe Brief Resolved Unexplained Event in a Newborn Infant in Association with Maternal Sertralin Treatment during Pregnancy.

Background: Selective serotonin reuptake inhibitors are a very common choice of antidepressive drug-therapy during pregnancy. In up to 30% of cases, they have been found to cause neonatal abstinence syndrome in newborn infants. Although often both time-limiting and self-limiting, severe symptoms of neonatal abstinence syndrome (NAS) can occur. Methods/Results: We report a term male infant suffering from a severe brief resolved unexplained event caused by his mother's sertraline intake during pregnancy. Conclusions: Newborn infants exposed to selective serotonine reuptake inhibitors (SSRIs) during pregnancy should be evaluated very carefully concerning NAS and monitored for NAS symptoms for a minimum of 72⁻96 h, or until symptoms have fully recovered using standardized protocols. There is a risk of severe NAS symptoms which might occur, and this circumstance should be discussed with the parents and taken into account before administering the drug.

Causes of hematochezia and hemorrhagic antibiotic-associated colitis in children and adolescents.

Diseases causing hematochezia range from benign to potentially life-threatening. Systematic pediatric data on the causes of hematochezia are scarce. We studied the underlying causes and long-term outcome of hematochezia in children. We further investigated the relevance of antibiotic-associated hemorrhagic colitis in children, especially if caused by Klebsiella oxytoca.Infants, children, and adolescents with hematochezia were recruited prospectively. Patients were grouped according to age (<1 year, 1-5 years, 6-13 years, >14 years). In addition to routine diagnostics, K oxytoca stool culture and toxin analysis was performed. We collected data on history, laboratory findings, microbiological diagnostic, imaging, final diagnosis, and long-term outcome.We included 221 patients (female 46%; age 0-19 years). In 98 (44%), hematochezia was caused by infectious diseases. Endoscopy was performed in 30 patients (13.6%). No patient died due to the underlying cause of hematochezia. The most common diagnoses according to age were food protein-induced proctocolitis in infants, bacterial colitis in young children, and inflammatory bowel disease in children and adolescents. Seventeen (7.7%) had a positive stool culture for K oxytoca. Antibiotic-associated colitis was diagnosed in 12 (5%) patients: 2 caused by K oxytoca and 2 by Clostridium difficile; in the remaining 8 patients, no known pathobiont was identified.Infections were the most common cause of hematochezia in this study. In most patients, invasive diagnostic procedures were not necessary. Antibiotic-associated hemorrhagic colitis caused by K oxytoca was an uncommon diagnosis in our cohort. Antibiotic-associated colitis with hematochezia might be caused by pathobionts other than C difficile or K oxytoca.

Even mild respiratory distress alters tissue oxygenation significantly in preterm infants during neonatal transition.

UNLABELLED: Near-infrared spectroscopy (NIRS) enables continuous non-invasive measurements of regional oxygen saturation (rSO2). The aim was to evaluate the dynamics of rSO2 of the brain, preductal and postductal tissues during postnatal transition in preterm infants with and without respiratory support (RS). This single-centre study was designed as an exploratory prospective observational study. Fifty one preterm infants (≥ 30 + 0 and < 37 + 0 weeks) delivered by caesarean section were included. RS using a T-Piece-Resuscitator and supplemental oxygen were given according to guidelines. NIRS measurements were carried out by using Invos Monitor (Covidien; USA) for the first 15 min of life. Three NIRS transducers were attached on the forehead (rSO2brain), the right forearm (rSO2arm) and the left lower leg (rSO2leg). Two groups were compared based on need for RS: normal transition (NT) and RS group. RESULTS: In NT group rSO2brain increased over time and was significantly higher than rSO2arm, whereas in RS group rSO2brain and rSO2arm increased without significant differences. Courses of rSO2arm and rSO2leg increased over time and showed a converging pattern with initially lower values of rSO2leg in NT group and a diverging pattern with lower levels of rSO2leg in RS group. Overall, rSO2 levels were higher in NT compared to RS group. CONCLUSION: Our findings indicate that the decreased rSO2 levels in RS group compared to NT group are not only caused by lower arterial oxygen saturation levels, but also by a compromised perfusion even in infants with only mild respiratory distress.

A left-to-right shunt via the ductus arteriosus is associated with increased regional cerebral oxygen saturation during neonatal transition.

BACKGROUND: Oxygen delivery to the brain is dependent on cardiac output and arterial oxygen content. OBJECTIVES: The study was designed to investigate the influence of a left-to-right shunt via the ductus arteriosus (DA) on regional oxygen saturation (rSO2) of the brain and peripheral tissue during postnatal transition. METHODS: Nested case-control study. In term neonates after elective cesarian section, rSO2 of the brain and pre- and postductal peripheral tissue were measured 15 min after uncomplicated postnatal transition. Two groups were formed according to shunt flow characteristics via the DA: shunt group (with a left-to-right shunt), and nonshunt group (no shunt). RESULTS: Of 80 infants, in 58 (72%) a left-to-right shunt was identified, and in 22 (28%) no flow was seen via the DA. The 22 infants formed the nonshunt group. They were matched with 22 newborn infants with a left-to-right shunt via the DA (shunt group). Infants in the nonshunt group had significantly lower cerebral rSO2 values and higher fractional tissue oxygen extraction and heart rate values. There were no significant differences in regard to peripheral rSO2 values. CONCLUSION: During postnatal transition, term infants with a left-to-right shunt via the DA have significantly higher cerebral rSO2 values compared to infants without shunt flow.

The influence of perinatal asphyxia on peripheral oxygenation and perfusion in neonates.

BACKGROUND: Perinatal asphyxia influences peripheral oxygenation and perfusion in neonates. OBJECTIVES: The aim was to investigate the influence of perinatal asphyxia on peripheral oxygenation and perfusion in neonates by using near-infrared spectroscopy (NIRS). METHODS: Prospective observational study. Neonates with gestational age >34 weeks and birth weight >2000 g without infection or congenital malformations were included. Peripheral muscle NIRS measurements in combination with venous occlusion were performed once in the first 48 h of life. Tissue oxygenation index (TOI), mixed venous oxygenation (SvO2), fractional oxygen extraction (FOE), haemoglobin flow (Hbflow), oxygen delivery (DO2) and oxygen consumption (VO2) were assessed. Furthermore arterial oxygen saturation, heart rate, blood pressure and temperatures were measured. Neonates with a UapH≤7.15 and an Apgar 5≤6 were compared to neonates with a UapH≥7.15, an Apgar 5≥7 (control group) and a UapH was correlated to NIRS parameters. RESULTS: 8 asphyxiated neonates were compared to 30 neonates in the control group. TOI (67.7±5.5%) and DO2 (29.0±14.2 µmol/100 mL/min) were significantly lower in asphyxiated neonates compared to the controls (TOI 71.8±4.9%, p=0.045; DO2 43.9±16.9 µmol/100 mL/min, p=0.028) and FOE was significantly higher (0.33±0.05) compared to the controls (0.28±0.06, p=0.028). Furthermore significant correlations between UapH and DO2 (r=0.78, p=0.022), VO2 (r=0.80, p=0.018) and FOE (r=-0.75, p=0.034) in the asphyxiated group were found. CONCLUSION: Peripheral oxygenation and perfusion measured with NIRS are compromised in neonates with perinatal asphyxia with worsening of parameters and degree of acidosis in the umbilical cord blood.