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Objectives To investigate how life-sustaining treatment (LST) decisions are made and identify problematic ethical concerns confronted by physicians and nurses in pediatric intensive care within Italy. Methods An 88-question online survey was created, based on a previous qualitative study conducted by this team. The survey was designed to identify how LST decisions were managed; contrasting actual practices with what participants think practices should be. Replies from physicians and nurses were compared, to identify potential inter-professional ethical tensions. The study also identified participants’ principal ethical concerns. Moreover, open-ended questions elicited qualitative perspectives on participants’ views. The survey was pilot-tested and refined before initiation of the study. Results 31 physicians and 65 nurses participated in the study. Participants were recruited from pediatric intensive care units across five Italian cities; i.e., Florence, Milan, Padua, Rome, Verona. Statistically significant differences were identified for (a) virtually all questions contrasting actual practices with what participants think practices should be and (b) 14 questions contrasting physician replies with those of nurses. Physicians and nurses identified the absence of legislative standards for LST withdrawal as a highly problematic ethical concern. Physicians also identified bearing responsibility for LST decisions as a major concern. Qualitative descriptions further demonstrated that these Italian pediatric intensive care clinicians encounter significantly distressing ethical problems in their practice. Conclusions The results of this study highlight a need for the development of (a) strategies for improving team processes regarding LST decisions, so they can be better aligned with how clinicians think decisions should be made, and (b) Italian LST decision-making standards that can help ensure optimal ethical practices.

Objective Families of ICU patients have a pressing need for information: they find themselves suddenly in a complex technical environment often because of a life-threatening illness of a loved one. Some evidence suggests that specific communication tools (like websites or brochures) could improve the experience of ICU families. Design Randomized, multicenter, stepped wedge trial for large-scale assessment of the effectiveness of a multitasking intervention to improve communication with families of critically ill patients. Main outcome: correct understanding of the prognosis. Secondary outcomes: correct understanding of medical treatments, prevalence of anxiety, depression and post-traumatic stress symptoms in the first ICU week. Prevalence of PTSD 6 months from ICU discharge. Empathy and burnout among ICU staff. Prevalence of refusals for tissues/organ donation, and medical claims. Subjects 2100 ICU relatives of critically ill patients. Interventions The intervention employs specific tools especially designed to raise the correctness of information and to improve the quality of communication: a website presenting the ICU world and justifying the relatives' emotions, with a webpage specifically dedicated to each participating ICU; a standard brochure; eight posters for the families' waiting room and a signboard for the ICU door. Measurements and main results The study plans to assess these materials in up to 300 Italian ICUs that will participate, according to a five waves program, each one with randomized starting order. This way the effect of the intervention will be evaluated simultaneously. Conclusion This is an educational study, aiming to spread good medical practices, while also verifying their real effectiveness in a large number of ICUs. Trial registration number: NCT03438175 .

Background Organ donation refusal from relatives of potential donors with brain death significantly reduces organ availability. The need for organ donation has increased over time, but the shortage of available donors is the major limiting factor in transplantation. We analyzed the impact of a new systematic communication approach between medical staff and patients' relatives on the rate of consent to organ donation. Methods The study was conducted as a single-center, non-randomized, controlled, before-and-after study at an 18-bed intensive care unit (ICU) of a university hospital. We compared the rate of consent for organ donation before and after the introduction of the new communication approach. Results A total of 291 brain-dead patients were studied. The consent rate increased from 71% in the pre-intervention period (2007–2012) to 78.4% in the post-intervention period (2013–2015), with an 82.75% increase in the 2014 to 2015 period. During these periods, no significant variation of consent to organ donation was recorded at the national and regional levels. Conclusions The introduction of a new communication approach between medical staff and relatives of brain-dead patients was associated with a significant increase in the rate of consent to donation. Our results highlight the importance of empathy with relatives in the ICU.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life-threating conditions still lacking a definite therapy and carrying a high mortality and morbidity, especially in children and infants. Albeit respiratory assistance and supportive therapies are crucial for ALI/ARDS, many drugs have been proposed to treat such syndromes through various mechanisms of action. On the whole the pharmacological therapy might play an important role in such a complex clinical situation but few evidence based data are available in pediatric and neonatal critical care. This review will focus on drugs directly available on the bedside, that is, medicines already administered in the practice or investigated in at least one clinical study. We will value the differences due to patient's age and the various causes of the syndrome, that may affect the response to the pharmacological therapy. A special attention will be given to the drugs directly deliverable into the lungs, as this strategy allows a total availability to the lung tissue. The experimental background behind each drug will be discussed and then clinical data in neonates and infants will be presented, if available. Data coming from adult critical care and thought to be somehow pertinent for the pediatric setting will otherwise be reviewed. Quality and evidence for or against each therapy will be evaluated according to the Scottish Intercollegiate Guidelines Network statement and practical reminders for clinicians will accordingly be provided.

Hypothermia may reduce the CO(2) production by decreasing the metabolism of the cooled tissue. We describe the first clinical use of hypothermia to lower hypercarbia in a case of bronchiolitis related respiratory failure unresponsive to maximal respiratory support. In this case, hypothermia allowed sparing the use of extracorporeal life support. Conclusion Hypothermia might be useful for severe acute respiratory failure unresponsive to aggressive respiratory support.

The frequency and distribution of acute intoxications and poisoning from non-pharmacological substances in children was evaluated in this observational-descriptive study. This was done by analyzing all admissions to the Emergency Room of our University in Rome during theperiod 1st January 2001 to 31st December 2012. We found 249 patients aged 0-14 years: 147 males and 102 females. The highest incidence occurred in the first 4 years of life: 44.2% in the 1-2 year age-group. Cases were mostly related to solvents (44.6%), natural products (17.7%), agricultural products (12.9%), corrosive acids and alkaline caustics(14.8%). Most admissions occurred during the time slot 18:00 to 21:00 (23.7%). No clinical symptoms were observed in 116 children (46.6% of the total), and physical examination was unrevealing. The remaining 133 displayed nausea/vomiting (22%) and pharyngeal hyperemia (18.8%). Laboratory tests and imaging studies were only performed in selected cases. In terms of consulting requests, the Poisons Center was contacted 156 times (62.6% of cases), the Pediatric Intensive Care Unit 38 times(15.2%), and the surgeon-endoscopist 18 times (7.2%). A short period of observation and monitoring in the Emergency Room was warranted in 106 children (42.5%). Gastroprotective drugs were used in 75 cases(30.1%) and activated charcoal in 18 (7.2%). Nintey-five children (38.2%) were admitted to the pediatric department , but no complications occurred. Targeted information programs in schools and during pediatric check-ups should decrease the risk of ingestion of non-pharmacological substances in children, and the costs of its management.

Aim: To show that conversion reactions should be suspected when symptomatology or instrumental checking does not conform to a precise pathological pattern in its anatomical and physiological keys. Methods: We report the case of a 14-y-old girl who presented with signs and symptoms of Guillain-Barre polyradiculonevritis. Negative instrumental and laboratory tests led us to consider a possible diagnosis of conversion reaction. Results: After a more detailed history emphasizing the close bond between the patient and her father, a poor peer-relation exchange and psychological stress, we were able to identify conversion reactions through the patient's motor signs. Conclusion: Conversion symptoms must be suspected and searched for when the neurologic outline is difficult to clarify, and also in the case of Guillain-Barre syndrome that does not respond to plasmapheresis.

Summary Objective To evaluate the correlation between cytokine and neurotrophin expression and clinical findings, disease severity, and outcome of children with H1N1 influenza infection. Methods A prospective observational clinical study was performed on 15 children with H1N1 infection, 15 controls with lower respiratory tract infections (LRTI), and 15 non-infected children. Plasma levels of interleukin (IL)-1β, IL-6, and neurotrophic factor (nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), and glial derived neurotrophic factor (GDNF)) were measured using immunoenzymatic assays. Results Significantly higher levels of IL-1β, IL-6, BDNF, and NGF were detected in patients with H1N1 infection compared to LRTI controls, while there was no significant variation in GDNF in the two groups. IL-1β, IL-6, BDNF, and NGF levels were significantly higher in H1N1 patients with more severe clinical manifestations compared to H1N1 patients with mild clinical manifestations. Of note, IL-6 was significantly correlated with the severity of respiratory compromise and fever, while NGF up-regulation was associated with the duration of cough. No correlation was found between interleukin and neurotrophic factor expression and outcome. Conclusions H1N1 infection induces an early and significant IL-1β, IL-6, BDNF, and NGF up-regulation. The over-expression of these molecular markers is likely to play a neuroimmunomodulatory role in H1N1 infection and may contribute to airway inflammation and bronchial hyper-reactivity in infected children.

The role of cytokines in relation to clinical manifestations, disease severity, and outcome of children with H1N1 virus infection remains thus far unclear. The aim of this study was to evaluate interleukin IL-1βand IL-6 plasma expressions and their association with clinical findings, disease severity, and outcome of children with H1N1 infection. We prospectively evaluated 15 children with H1N1 virus infection and 15 controls with lower respiratory tract infections (LRTI). Interleukin plasma levels were measured using immunoenzymatic assays. Significantly higher levels of IL-1βand IL-6 were detected in all patients with H1N1 virus infection compared to controls. It is noteworthy to mention that in H1N1 patients with more severe clinical manifestations of disease IL-1βand IL-6 expressions were significantly upregulated compared to H1N1 patients with mild clinical manifestations. In particular, IL-6 was significantly correlated with specific clinical findings, such as severity of respiratory compromise and fever. No correlation was found between interleukin expression and final outcome. In conclusion, H1N1 virus infection induces an early and significant upregulation of both interleukins IL1βand IL-6 plasma expressions. The upregulation of these cytokines is likely to play a proinflammatory role in H1N1 virus infection and may contribute to airway inflammation and bronchial hyperreactivity in these patients.

To verify the feasibility of non-invasive ventilation (NIV) in immunocompromised children affected by ARDS.University Hospital PICU.Twenty-three consecutive immunocompromised children treated with NIV for ARDS.All consecutive patients received NIV through a face-mask or a helmet.No differences were found regarding admission data and severity scores between NIV responders and non-responders. Early and sustained improvement in PaO2/FiO2 ratio were observed in 82 and 74% of cases, respectively. 13 out of 23 patients (54.5%) avoided intubation and were discharged from the PICU; ten patients required intubation: two of them survived and eight patients died (two refractory hypoxemia, three septic shock, three multi-organ failure). PICU and intra-hospital mortality was significantly higher for NIV-nonresponders (P0.001). PICU stay was significantly shorter for NIV responders (P = 0.03). NIV responders had significantly lower heart and respiratory rate at the end of treatment (P0.001 and P = 0.048, respectively).NIV administration is feasible and well tolerated in immunocompromised children with ARDS. A short NIV trial can be used to verify the usefulness of the technique. A randomized controlled trial is needed to confirm the efficacy of NIV in immunocompromised children requiring ventilatory support for ARDS.

Status dystonicus (SD) is a life threatening disorder that develops in patients with both primary and secondary dystonia, characterized by acute worsening of symptoms with generalized and severe muscle contractions. To date, no information is available on the best way to treat this disorder. We review the previously described cases of SD and two new cases are reported, one of which occurring in a child with static encephalopathy, and the other one in a patient with pantothenate kinase-associated neurodegeneration. Both patients were admitted to an intensive care unit and treated with midazolam and propofol. This approach proved to be useful in the former while the progressive nature of the dystonia of the second patient required the combination of intrathecal baclofen infusion and bilateral pallidal deep brain stimulation. We believe that a rapid and aggressive approach is justified to avoid the great morbidity and mortality which characterize SD. Our experience, combined with the data available in the literature, might permit to establish the best strategies in managing this rare and severe condition.

We describe for the first time a case of macrophage activation syndrome in a child with hyperimmunoglobulinemia D with periodic fever syndrome who required intensive care support. Up-regulated monokine production, high serum levels of triglycerides and ferritin, clotting abnormalities with hypofibrinogenemia, and rapidly evolving pancytopenia should alert the clinician to the possible diagnosis of macrophage activation syndrome, even in autoinflammatory diseases characterized basically by the periodic recurrence of unprovoked inflammatory attacks. Bone marrow aspiration showing well-differentiated macrophages phagocytosing hematopoietic elements remains the main tool for a final diagnosis, and cyclosporine is the best strategy for treatment.

We describe our second clinical observation of pulmonary injury after a "liquid ecstasy" ingestion/inhalation by a 3-year-old girl. Apart from the deep coma state, a markedly asymmetric pulmonary compromise was recorded. A transient coagulation activation was detected, possibly triggered off by the toxic effect on the lung alveolar-capillary membrane.

Objectives: Our aim was to analyze prognostic factors and their association with outcome among children with severe head injury. Methods: We conducted a retrospective study among children with severe head injury admitted to our Pediatric Intensive Care Unit (PICU) from November 1992 to December 2000. The patients were immediately evaluated for the severity of head injury (Glasgow Coma Score, GCS), clinical presentation, cerebral axial tomography, early complications (hypoxia and hypotension), metabolic and hematological alterations and early post-traumatic seizures. Six months after injury we applied the Glasgow Outcome Score (GOS). Correlations with GOS were evaluated using univariate and multivariate logistic models. Results: In all, 122 children with severe head injury were identified. The patients presented the following scores: 18 (14.7.0%) children had a GOS of 1; 2 had a GOS of 2 (1.6%); 27 (22.2%) a GOS of 3 and 75 (61.5%) a GOS of 4 or 5. A low GOS was significantly and independently associated with low GCS, multiple trauma, the presence of hypoxia and hypotension, disseminated intravascular coagulation (DIC), hyperglycemia and early post-traumatic seizures. Hematological alterations (white blood cells) were also associated with a low GOS, though not significantly. Conclusion: In addition to GCS, types of trauma and brain lesion, hypoxia and hypotension, hemocoagulative disorders (DIC), hyperglycemia and early post-traumatic seizures are predictors of GOS. A knowledge of these prognostic factors and the correct management of children with severe head injury helps clinicians to improve outcome and to reduce morbidity and mortality.

Background and Aims In the last years the world has been facing a new pandemic caused by a H1N1 influenza virus, showing particular virulence in children. Cytokines and neurotrophic factors seem to play an important role in severity and progression of this infection. In our study we evaluate cytokine (IL-1b and IL-6) and neurotrophic factor [Nerve Growth Factor (NGF), Brain Derived Neurotrophic Factor (BDNF), and Glial Derived Neurotrophic Factor (GDNF)] expression and their association with clinical-laboratory findings and outcome of children with H1N1 influenza virus infection. Methods We performed a prospective observational clinical study on 15 children with H1N1 influenza virus infection and 15 controls with lower respiratory tract infection (LRTI). Cytokines and neurotrophic factor plasma levels were measured using an immunoenzymatic assay. Results Significantly higher plasma levels of IL-1b, IL-6, NGF and BDNF were demonstrated in all patients with H1N1 infection respect to controls, while GDNF plasma levels did not undergo significant variations in the two groups. IL-6, NGF and BDNF expression was also significantly correlated with some laboratory and clinical findings, such as fever, cough, specific radiological lesions, and platelet count. No correlation was found between interleukin and neurotrophic factor expression and final outcome. Conclusions H1N1 virus infection induces an early and significantly up-regulation of both interleukins (IL1b and IL-6) and neurotrophic factors (BDNF and NGF) respect to LRTI patients. The overexpression of these molecular markers is likely to play a neuro-immunomodulatory role in H1N1 infection and may contribute to airway inflammation and disease severity and progression.

Acute respiratory distress syndrome (ARDS) is characterized by damage to the arteriolar-capillary endothelium and alveolar epithelium that leads to surfactant deficiency and atelectasis. Alveolar collapse and pulmonary edema will further induce surfactant inactivation. Surfactant supplementation has been suggested but results are unpredictable. Poor response may be due to inhibition of administered surfactant by plasma components filling the alveolar space, severity of lung injury, time of surfactant application and inadequate dose. We report the course of gas exchange and pulmonary mechanics after instillation of surfactant in 14 children (3 months-7 years) with severe ARDS, defined as an oxygenation index (OI) > 30 and a partial pressure of oxygen/ fraction of Inspired oxygen (PaO2/FiO2) 200 for more than 12 hours. Diluted surfactant lung lavages were able to increase blood gas exchange in all our patients despite previously severe gas exchange impairment.

Sir: We read with great interest the article from Piastra et al. [3] describing three cases of Anomalous Left Coronary Artery Arising from the Pulmonary Artery (ALCAPA) simulating a bronchiolitis. The article is interesting since it focuses on a congenital anomaly that can easily be misdiagnosed. However, it proposes an approach to avoid error that – in our view – would not be effective. Concerning the implantation of “ ...a training programme to favour limited echocardiography learning by the emergency physicians...”, we consider that the likelihood that such a specialist would be able to diagnose ALCAPA with reliability is unrealistic. Indeed, and as the authors controversially state in their abstract, “...paediatric cardiological evaluation with twodimensional echocardiography may eventually reveal this rare condition, whereas cardiac catheterisation remains the standard means of diagnosis...”. This statement illustrates how difficult it still is to clearly diagnose aberrant origin and course of the coronary artery even by an experienced paediatric cardiologist, and particularly whenever associated with other cardiac lesions simulating a normal physiological scenario [1, 2, 4] Thus, it seems too optimistic to allude that emergency physicians will be skilled enough to do so. Chest X-ray should remain mandatory, and as a matter of fact, a toddler with a suspected non-respiratory wheezing condition and a cardiomegaly, mostly if presenting with signs of circulatory failure, should systematically also have an electrocardiogram with the objective of revealing ischaemic changes evocating the diagnosis as well as echocardiography performed by a paediatric cardiologist, since many other entities other than ALCAPA might induce a dilated hypokynetic cardiomyopathy with similar clinical features: late-diagnosed aortic coarctation, primary cardiomyopathy, myocarditis, sustained arrhythmias, to mention some. The cardiologist would then, based upon the iconographic quality of the echocardiography, decide the need for the cardiac catheterisation. Last, but not least, one should not forget that ALCAPA and a bronchiolitis-like syndrome may co-exist in a same patient, all the more that the first might be unmasked by the last. Eduardo da Cruz, MD Yacine Aggoun, MD Cecile Tissot-Daguette, MD Maurice Beghetti, MD