Sudden Onset of Severe Pulmonary Hypertension in a Preterm Infant: A Case Report on the Role of Maternal Use of Serotonin Re-Uptake Inhibitors During Pregnancy and Concurrent Risk Factors.

Persistent pulmonary hypertension of the newborn (PPHN) is a severe condition caused by failed circulatory adaptation at birth. Pulmonary hypertension is most common in full-term infants and rare in preterms, although it is increasingly diagnosed also in extremely preterm infants. Previous studies demonstrated the association between maternal use of selective serotonin re-uptake inhibitors during gestation and pulmonary hypertension. This brief report describes the complex physiopathological correlations that were identified in a case of severe pulmonary hypertension in a fetal growth restricted (FGR) preterm infant, with a history of maternal use of antidepressants during pregnancy. Perinatal factors, triggers and aggravating mechanisms caused a dramatic clinical course. Maternal history of escitalopram therapy throughout pregnancy was noted. Uteroplacental insufficiency, fetal hypoxia, FGR, preeclampsia, preterm delivery, antenatal steroids, and cesarean section were documented as concurrent risk factors. Myocardial immaturity and dysfunction, secondary to FGR and prematurity aggravated the hemodynamic compromise. The short time gap between pharmacological ductal closure and the onset of PPHN may suggest a cause-effect relationship, as observed in previous reports. Placental histopathologic findings are reported.

Moral Distress in Healthcare Providers Who Take Care of Critical Pediatric Patients throughout Italy-Cultural Adaptation and Validation of the Italian Pediatric Instrument.

BACKGROUND: Although Moral Distress (MD) is a matter of concern within the Pediatric Intensive Care Unit (PICU), there is no validated Italian instrument for measuring the phenomenon in nurses and physicians who care for pediatric patients in Intensive Care. The authors of the Italian Moral Distress Scale-Revised (Italian MDS-R), validated for the adult setting, in 2017, invited further research to evaluate the generalizability of the scale to clinicians working in other fields. Our study aims to reduce this knowledge gap by developing and validating the pediatric version of the Italian MDS-R. METHODS: We evaluated the new instrument for construct validity, then we administered it in a multicenter, web-based survey that involved healthcare providers of three PICUs and three adult ICUs admitting children in northern, central, and southern Italy. Finally, we tested it for internal consistency, confirmatory factorial validity, convergent validity, and differences between groups analysis. RESULTS: The 14-item, three-factor model best fit the data. The scale showed good reliability (a = 0.87). Still, it did not correlate with the Emotional Exhaustion and Depersonalization sub-scales of the Maslach Burnout Inventory (MBI) or with the 2-item Connor-Davidson Resilience Scale (CD-RISC 2) or the Satisfaction with Life Scale (SWLS). A mild correlation was found between the Italian Pediatric MDS-R score and intention to resign from the job. No correlation was found between MD and years of experience. Females, nurses, and clinicians who cared for COVID-19 patients had a higher MD score. CONCLUSIONS: The Italian Pediatric MDS-R is a valid and reliable instrument for measuring MD among Italian health workers who care for critically ill children. Further research would be helpful in better investigating its applicability to the heterogeneous scenario of Italian Pediatric Critical Care Medicine.

COVID-19 Pneumomediastinum: Possible Role of Transesophageal Echo in Bedside Percutaneous Bicaval Double-Lumen ECMO Cannulation in Children. A Case Report.

COVID-19 is generally uneventful in children. Only 8% of severe acute respiratory distress syndrome corona virus 2 pediatric patients require intensive care; of these, 1% may need extracorporeal membrane oxygenation. Preexisting medical conditions are an independent risk factor for pediatric intensive care unit admission. We describe the case of an 11-year-old girl with adenosine deaminase 2 deficiency who presented severe COVID-19 acute respiratory distress syndrome, complicated by a massive air leak syndrome. The respiratory failure, refractory to conventional support, required veno-venous extracorporeal membrane oxygenation. To prevent viral diffusion, bicaval double-lumen cannulation was performed percutaneously at the bedside under exclusive echo guidance. Because of pneumomediastinum, pneumothorax, and subcutaneous emphysema, ultrasound visualization of the heart was possible only with transesophageal echo. To our knowledge, this is the first description of a transesophageal echo guided bedside percutaneous bicaval double-lumen extracorporeal membrane oxygenation cannulation in a pediatric patient. Pitfalls of the technique are highlighted.

Working as a team in airway surgery: History, present and perspectives.

Teamwork is one of the most important trend in modern medicine. Airway team were created in many places to respond in a multidisciplinary and coordinated way to challenging clinical problems which were beyond the possibility of an individual management. In this chapter, we illustrate the historical steps leading to the development of an airway team in a pediatric referral hospital, describe the present teamwork activity defining the key points for the creation of a team and discussing different organization models; finally we delineate possible future directions for the airway teams in the globalized world.

Delivery Room Intensive Care Unit: 5 Years' Experience in Assistance of High-Risk Newborns at a Referral Center.

Objective: The aim of the study is to describe a delivery room intensive care unit (DRICU) model and evaluate its effectiveness in preventing morbidity and mortality in high-risk newborns. Design: This retrospective case series includes all DRICU procedures performed from 2016 to 2020. Setting: Gaslini Children's Hospital is a major pediatric tertiary care center where high-risk pregnancies are centralized. The Neonatal and Pediatric Intensive Care Unit admits every year about 100 high-risk newborns. Patients: The selected patients are newborns at risk of critical conditions immediately after birth for respiratory or cardiovascular congenital disorders. Interventions: The perinatal plan is defined by the multidisciplinary team of Fetal and Perinatal Medicine. The DRICU procedure provides highly specialized care through a protocol that includes logistics, personnel, equipment, and clinical pathways. Main Outcome Measures: The primary outcome is the prevention of acute complications and mortality in the delivery room and early neonatal period. Results: From 2016 to 2020, 40 DRICU procedures were performed. The main prenatal diagnoses included congenital heart disease with a high risk of life-threatening events immediately after birth (38%), congenital diaphragmatic hernia (35%), and fetal hydrops/hydrothorax (23%). Mean gestational age was 35.9 weeks (range: 31-39), and mean birth weight was 2,740 grams (range: 1,480-3,920). DRICU assistance completed in all patients by neonatal intensivists included tracheal intubation and arterial and central venous cannulation; complex procedures such as ex-utero intrapartum technique and extracorporeal membrane oxygenation cannulation are described. No deaths nor severe acute complications occurred in the delivery room or in the immediate postnatal period. Conclusions: The outcome in critical newborns is potentially affected by planned assistance strategies and specialized competencies through the implementation of a DRICU protocol.

Focal status and acute encephalopathy in a 13-year-old boy with de novo DNM1L mutation: Video-polygraphic pattern and clues for differential diagnosis.

BACKGROUND: Pathogenic variants in the dynamin 1 like gene are related to abnormal mitochondrial dynamics and distributions and are associated to variable clinical phenotypes. A few patients harboring the p.Arg403Cys missense variant appears to be different from the classical, more severe phenotypes, showing sudden onset of drug resistant seizures after a previously normal or slightly delayed development. CASE REPORT: We report on a boy with abrupt onset of focal status and coma at the age of 13, initially treated as autoimmune encephalitis, with final diagnosis of de novo missense p.Arg403Cys variant in the DNM1L gene. DISCUSSION: We compare his clinical, electrophysiological, biochemical, neuroradiological and histopathological picture to the rare cases reported to date and provide diagnostic clues that can help clinicians in differentiate p.Arg403Cys-related phenotype from that of immune-mediated encephalopathies. CONCLUSION: The clinical picture related to p.Arg403Cys mutations should be considered alongside acquired pathologies in the differential diagnosis of young patients with focal refractory epilepsy and encephalopathy, also occurring during late childhood or adolescence. Prompt genetic testing allows to avoid unnecessary treatments and procedures and to better define the prognosis and management strategies.

Intensivists Performed Percutaneous Bicaval Double-Lumen Echo-Guided Extracorporeal Membrane Oxygenation Cannulation at Bedside in Newborns and Children: A Retrospective Analysis.

OBJECTIVES: To describe a single institution experience on echo-guided percutaneous bicaval double lumen extracorporeal membrane oxygenation cannulation performed at the bedside by intensivists. DESIGN: Retrospective observational study. SETTING: Extracorporeal membrane oxygenation team of a tertiary care children's hospital. PATIENTS: All patients 0-14 years old undergoing venovenous extracorporeal membrane oxygenation from January 1, 2013, to January 1, 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Thirty children underwent 32 extracorporeal membrane oxygenation runs. Median age at enrollment was 2 months (interquartile range, 0-20.5 mo), 65.6% of the runs (21 patients) were performed in newborns (n = 13, 40.6%) or infants (n = 8, 25%). Median preextracorporeal membrane oxygenation index was 66.9 (interquartile range, 50-85.6). Major comorbidities were present in 50% of patients. All patients were cannulated percutaneously. In two cases cannulation occurred from the left internal jugular vein. Extracorporeal membrane oxygenation was effective in increasing pH, arterial oxygen saturation, PaO2, and lowering PaCO2. The overall differences in pre and postextracorporeal membrane oxygenation values were statistically significant, while stratifying patients according to the cannula diameter (mm)/major diameter of the cannulated internal jugular vein (mm) ratio (> 0.67 or ≤ 0.67), statistical significance was reached only for the highest ratio. Complications were observed in three runs: two cannula tip dislocations in the right atrium and one limited flow in the only case in which an Avalon cannula was not used. In 20 cases (62.5% of 32 runs), the cannulated vessel was patent at follow-up or autopsy. A ratio less than or equal to 0.67 or greater than 0.67 did not influence the occurrence rate of complications, nonpatency of the internal jugular vein, death for intracranial bleeding and death at 30 days from extracorporeal membrane oxygenation discontinuation. Overall cumulative survival at 30 days from extracorporeal membrane oxygenation discontinuation was 60% (95% CI, 40-75), with a survival advantage in the case of ratio greater than 0.67 (65%; 95% CI, 44-80 vs 25%; 95% CI, 0-60). CONCLUSIONS: The described technique proved to be feasible, safe, and effective. Further investigation is needed.

Epidemiology of Infectious Complications During Extracorporeal Membrane Oxygenation in Children: A Single-Center Experience in 46 Runs.

BACKGROUND: Infections represent a severe complication of extracorporeal membrane oxygenation (ECMO). Aim of the present study was to describe the epidemiology of infections acquired during ECMO in a tertiary care children's hospital. METHODS: Retrospective analysis of clinical records of patients undergoing ECMO between January 2009 and December 2016. For each patient, data were collected on clinical characteristics, modality of ECMO support, site and etiology of documented infections, survival within 1 week after ECMO weaning and/or at pediatric intensive care unit discharge. These data were employed to evaluate overall infection prevalence, infection rate expressed as episodes/1000 days of support and cumulative risk estimates of infections occurring during ECMO. RESULTS: During the study period, a total of 46 ECMO procedures were performed. The overall prevalence of documented infections was 33%, with an infection rate of 27.22 and a cumulative risk of 55%. Bloodstream infection represented the most frequently documented (53%), followed by pneumonia (40%). Coagulase-negative staphylococci and Pseudomonas aeruginosa prevailed as isolated pathogens. Overall survival was 59%, and 46% among those developing infections during ECMO. CONCLUSIONS: ECMO is a procedure at high risk for infections. Our data, limited to 1 center, represent a recent benchmark for further investigations.

Ofatumumab-associated acute pneumonitis: Not new but still the first case.

Ofatumumab is an anti-CD20 humanized monoclonal antibody utilized in the treatment of several clinical conditions resistant to other treatments. In spite there was a general expectation that ofatumumab was less toxic compared to rituximab, side effects have been reported that resemble those of its anti-CD20 chimeric precursor. Here, we describe the first case of Ofatumumab associate lung injury occurring in a 14-year-old boy affected by nephrotic syndrome dependent to prednisone plus cyclosporine A who had been treated with the dose of drug utilized in nephrotic syndrome (1500 mg/173 m2). The patient developed the full blown picture of rituximab associated lung injury (RALI) after 45 days from ofatumumab infusion at the end of the steroid tapering: severe exertional dyspnea, mild fever and cyanosis, with CT scan showing diffuse ground glass areas in both lungs and DLCO (diffusing capacity of transfer factor of the lung for carbon monoxide) test suggestive for reduction of CO diffusion. Clinical outcome was good with rapid improvement and normalization of all parameters without any specific therapy. After 60 days, chest CT and CO diffusion tests were normal. In conclusion, we describe here the first case of acute pneumonitis associated with ofatumumab that presents the same clinical, laboratory, and radiology features of the lung injury reported for rituximab. Like RALI occurring in patients treated for nephrotic syndrome, this case had a mild clinical expression and recovered in a few months.

Emergency percutaneous, bicaval double-lumen, ECMO cannulation in neonates and infants: insights from three consecutive cases.

BACKGROUND: Veno-venous extracorporeal membrane oxygenation (ECMO) is probably the preferable configuration to assist children with respiratory failure who do not respond to maximized conventional therapies. The single-vessel, double-lumen approach through the internal jugular vein is extremely advantageous, especially in infants, where femoral access presents limitations related to the small dimensions of the veins. In case of emergencies, ECMO might need to be started at the bedside, without the availability of fluoroscopic guidance. To our knowledge, a completely percutaneous approach has not been reported before in children younger than 1 year and weighing less than 5 kg. METHODS: We describe 3 cases of emergency bedside, percutaneous, bicaval double-lumen cannulation under real-time transthoracic ultrasound control in 2 neonates and 1 infant. RESULTS: In our experience, this approach proved to be safe, effective and time saving, while minimizing bleeding from the cannula insertion site. Cannulation times, from decision making to the beginning of ECMO flow, were 30, 28, 25 minutes respectively, from patient 1 to 3. We do not report any cannula-related injury to vessels and heart structures. CONCLUSIONS: Our preliminary data suggest that, with the described precautions, percutaneous, echo-guided, bicaval double-lumen cannulation in neonates and infants could be effective and free from major complications. Further evaluation should be warranted in the neonatal population.

Incidence of pain after craniotomy in children.

BACKGROUND: There is very few information regarding pain after craniotomy in children. OBJECTIVES: This multicentre observational study assessed the incidence of pain after major craniotomy in children. METHODS: After IRB approval, 213 infants and children who were <10 years old and undergoing major craniotomy were consecutively enrolled in nine Italian hospitals. Pain intensity, analgesic therapy, and adverse effects were evaluated on the first 2 days after surgery. Moderate to severe pain was defined as a median FLACC or NRS score ≥ 4 points. Severe pain was defined as a median FLACC or NRS score ≥ 7 points. RESULTS: Data of 206 children were included in the analysis. The overall postoperative median FLACC/NRS scores were 1 (IQR 0 to 2). Twenty-one children (16%) presented moderate to severe pain in the recovery room and 14 (6%) during the first and second day after surgery. Twenty-six children (19%) had severe pain in the recovery room and 4 (2%) during the first and second day after surgery. Rectal codeine was the most common weak opiod used. Remifentanil and morphine were the strong opioids widely used in PICU and in general wards, respectively. Longer procedures were associated with moderate to severe pain (OR 1.30; CI 1.07-1.57) or severe pain (OR 1.41; 1.09-1.84; P < 0.05). There were no significant associations between complications, pain intensity, and analgesic therapy. CONCLUSION: Children receiving multimodal analgesia experience little or no pain after major craniotomy. Longer surgical procedures correlate with an increased risk of having postoperative pain.

Intensive care unit admission in children with malignant or nonmalignant disease: incidence, outcome, and prognostic factors: a single-center experience.

OBJECTIVE: To investigate pediatric intensive care unit (PICU) admission in children with malignant and nonmalignant diseases who developed life-threatening complications. PATIENTS AND METHODS: Between 1999 and 2010, of the 1278 eligible pediatric patients treated for a malignant or nonmalignant disease, 54 were admitted to the PICU for respiratory distress (40.7%), neurological events (33.3%), severe sepsis (14.8%), and organ failure (11.2%). RESULTS: Rate of PICU admission was 4.2%, with a 2-year cumulative incidence of 4.5%. Risk factors associated with higher cumulative incidence of PICU admission were older age at study entry (P=0.003), nonmalignant underlying disease (P=0.015), and hematopoietic stem cell transplantation (P<0.001). Patients with leukemia/lymphoma were more likely to be admitted to the PICU compared with patients with solid tumors (P<0.001). Patients admitted because of organ failure had the highest frequency of death within 90 days. Factors significantly associated with survival at 90 days from PICU admission included: no mechanical ventilation (P<0.001), nonmalignant underlying disease (P=0.030), and year of PICU admission after 2005 (P=0.038). CONCLUSIONS: Nonmalignant disease and use of alternative hematopoietic stem cell transplantation were associated with higher risk of PICU admission. Close cooperation between hematologists and intensivists and definition of criteria for PICU admission and discharge contributed to increase in survival of these patients.

Noninvasive ventilation and low-flow veno-venous extracorporeal carbon dioxide removal as a bridge to lung transplantation in a child with refractory hypercapnic respiratory failure due to bronchiolitis obliterans.

OBJECTIVE: To report the successful management of end-stage hypercapnic respiratory failure through the association of noninvasive mechanical ventilation and a novel automated device (Decapsmart) of low-flow veno-venous extracorporeal CO2 removal. DESIGN: Case report. SETTINGS: Pediatric intensive care unit at a tertiary care children's hospital. PATIENT: A pediatric patient affected by bronchiolitis obliterans with refractory hypercapnic respiratory failure. The patient received successful lung transplantation after respiratory support with noninvasive mechanical ventilation and a novel automated device of low-flow veno-venous extracorporeal CO2 removal. INTERVENTIONS: Treatment of end-stage hypercapnic respiratory failure with the association of noninvasive ventilation and low-flow veno-venous extracorporeal CO2 removal as a bridge to lung transplantation. MEASUREMENTS AND MAIN RESULTS: Respiratory support controlling hypercapnia, limiting volutrauma, barotraumas, and preventing the incidence of ventilator-associated pneumonia/lung colonization. CONCLUSION: Noninvasive mechanical ventilation and Decapsmart have proven efficacious in managing refractory hypercapnic respiratory failure in a pediatric patient awaiting lung transplantation.

Spinal anaesthesia in paediatric patients.

PURPOSE OF REVIEW: Spinal anaesthesia has seldom been employed in paediatric patients. Its use has been suggested mainly in former preterm newborns and infants who are known to be exposed to high perioperative apnoea risk. There is currently some evidence that spinal anaesthesia could be considered as an equal alternative to general anaesthesia as it is in adults. RECENT FINDINGS: New drugs and adjuvants recently introduced in clinical practice, more-detailed knowledge of spread anaesthetic modalities and larger databases, now available, could today make paediatric spinal anaesthesia a more suitable technique for many anaesthetists. SUMMARY: We will review recent literature focusing the latest techniques, drugs, dosages, and complications in order to define the limits and advantages of employing spinal anaesthesia in all paediatric ages, in routine and emergency surgery.

Use of spinal anaesthesia in paediatric patients: a single centre experience with 1132 cases.

BACKGROUND: Spinal anaesthesia has been used in children for over 100 years and in the last two decades its popularity for newborns and infants has increased, but there are still unanswered questions with the technique. METHODS: We evaluated the characteristics of spinal block including ease of performance, efficacy, adverse effects and complications in 1132 children, aged 6 months to 14 years, undergoing surgery in the lower part of the body. Local ethical committee approved the protocol of this prospective study, and parents gave written informed consent and older children their assent. All patients were sedated with midazolam, thiopental or propofol intravenously during spontaneous ventilation. No inhalation anaesthetics were used. Spinal block was performed with 0.5% hyperbaric bupivacaine at a dose of 0.2 mg x kg(-1). RESULTS: Efficacy, safety and ease of performance of the spinal block were shown to be satisfactory in most children. Only 27 of the 1132 children needed any supplementation. The incidence and severity of complications was low. Only nine of 942 children, < 10 years of age and eight of 190 children, 10 years or older, developed hypotension. The incidences of postdural puncture headache, in five of the 1132 children, and backache, in nine of the 1132, were low. No other neurological complications were reported. CONCLUSIONS: Spinal anaesthesia with hyperbaric bupivacaine is a feasible anaesthetic method in children for surgery in the lower part of the body.