Severe diaphragmatic dysfunction with preserved activity of accessory respiratory muscles in a critically ill child : a case report of failure of neurally adjusted ventilatory assist (NAVA) and successful support with pressure support ventilation (PSV)

BACKGROUND: Neurally adjusted ventilatory assist (NAVA) is an alternative to pressure support ventilation (PSV) potentially improving patient-ventilator interaction. During NAVA, diaphragmatic electrical activity (EAdi) is used to trigger the ventilator and perform a proportional respiratory assistance. We present a case in which the presence of severe bilateral diaphragmatic dysfunction led to a failure of NAVA. On the contrary, the preserved activity of the accessory inspiratory muscles allowed a successful respiratory assistance using PSV. CASE PRESENTATION: A 10-year-old girl developed quadriplegia after neurological surgery. Initially, no spontaneous breathing activity was present and volume controlled ventilation was necessary. Two months later spontaneous inspiratory efforts were observed and a maximal negative inspiratory force of -\u200920 cmH2O was recorded. In addition, a NAVA nasogastric tube was placed. The recorded EAdi signal, despite showing a phasic activity, had a very low amplitude (1-2\u2009\u3bcV). Two brief (15\u2009min) breathing trials to compare PSV (pressure support\u2009=\u20098 cmH2O) with NAVA (Gain\u2009=\u20095 cmH2O/\u3bcV, inspiratory trigger\u2009=\u20090.3\u2009\u3bcV) were performed. On PSV, the patient was well adapted with stable tidal volumes, respiratory rates, minute ventilation, end-tidal and venous carbon dioxide levels. When switched to NAVA, her breathing pattern became irregular and she showed clear sign of increased work of breathing and distress: tidal volume dropped and respiratory rate rose, leading to an increase in total minute ventilation. Nevertheless, end-tidal and venous carbon dioxide rapidly increased (from 49 to 55\u2009mmHg and from 52 to 57\u2009mmHg, respectively). An electromyographic study documented an impairment of the diaphragm with preserved activity of the accessory inspiratory muscles. CONCLUSIONS: We document the failure of mechanical assistance performed with NAVA due to bilateral diaphragmatic dysfunction in a critically ill child. The preserved activity of some accessory respiratory muscles allowed to support the patient effectively with pressure support ventilation, i.e. by applying a pneumatic trigger. The present case underlines (i) the importance of the integrity of the respiratory centers, phrenic nerves and diaphragm in order to perform NAVA and (ii) the possible diagnostic role of EAdi monitoring in complex cases of weaning failure

Nusinersen treatment and cerebrospinal fluid neurofilaments : An explorative study on Spinal Muscular Atrophy type 3 patients

The antisense oligonucleotide Nusinersen has been recently licensed to treat spinal muscular atrophy (SMA). Since SMA type 3 is characterized by variable phenotype and milder progression, biomarkers of early treatment response are urgently needed. We investigated the cerebrospinal fluid (CSF) concentration of neurofilaments in SMA type 3 patients treated with Nusinersen as a potential biomarker of treatment efficacy. The concentration of phosphorylated neurofilaments heavy chain (pNfH) and light chain (NfL) in the CSF of SMA type 3 patients was evaluated before and after six months since the first Nusinersen administration, performed with commercially available enzyme-linked immunosorbent assay (ELISA) kits. Clinical evaluation of SMA patients was performed with standardized motor function scales. Baseline neurofilament levels in patients were comparable to controls, but significantly decreased after six months of treatment, while motor functions were only marginally ameliorated. No significant correlation was observed between the change in motor functions and that of neurofilaments over time. The reduction of neurofilament levels suggests a possible early biochemical effect of treatment on axonal degeneration, which may precede changes in motor performance. Our study mandates further investigations to assess neurofilaments as a marker of treatment response

Acute myeloid leukemia and pregnancy: Clinical experience from a single center and a review of the literature

Background: Acute myeloid leukemia (AML) accounts for more than two thirds of leukemia during pregnancy and has an incidence of 1 in 75,000 to 100,000. Its clinical management remains a challenging therapeutic task both for patient and medical team, given to the therapy-attributable risks for mother and fetus and the connected counseling regarding pregnancy continuation. Methods: We provided a review of updated literature and a comprehensive description of five maternal/fetal outcomes of AML cases diagnosed concomitantly to pregnancy and treated at our Institution from 2006 to 2012. Results: Median age at AML diagnosis was 32 years (31-39). One diagnosis was performed in first trimester and the patient asked for therapeutic abortion before starting chemotherapy. Three cases were diagnosed in second/third trimester; in one case leukemia was diagnosed concomitantly with intrauterine fetal death, while the remaining two patients continued pregnancy and delivered a healthy baby by cesarean section. In only one of these two cases chemotherapy was performed during pregnancy (at 24 + 5 weeks) and consisted of a combination of daunorubicine and cytarabine. Therapy was well tolerated and daily fetus monitoring was performed. After completion of 30 weeks of gestation a cesarean section was carried out; the newborn had an Apgar score of 5/1'-7/5'-9/10', oxygen therapy was temporarily given and peripheral counts displayed transient mild leukopenia. One patient had diagnosis of myelodysplastic syndrome rapidly progressed to AML after delivery. Four out of the 5 described women are currently alive and disease-free. Three children were born and long-term follow-up has shown normal growth and development. Conclusions: The treatment of AML occurring during pregnancy is challenging and therapeutic decisions should be taken individually for each patient. Consideration must be given both to the immediate health of mother and fetus and to long-term infant health. Our series confirmed the literature data: fetal toxicity of cytostatic therapy clusters during the first trimester; while chemotherapy can be administered safely during second/third trimester and combination of daunorubicin and cytarabine is recommended for induction

Pediatric Intensive Care Unit admission criteria for haemato-oncological patients: a basis for clinical guidelines implementation

Recent advances in supportive care and progress in the development and use of chemotherapy have considerably improved the prognosis of many children with malignancy, thus the need for intensive care admission and management is increasing, reaching about 40% of patients throughout the disease course. Cancer remains a major death cause in children, though outcomes have considerably improved over the past decades. Prediction of outcome for children with cancer in Pediatric Intensive Care Unit (PICU) obviously requires clinical guidelines, and these are not well defined, as well as admission criteria. Major determinants of negative outcomes remain severe sepsis/septic shock association and respiratory failure, deserving specific approach in children with cancer, particularly those receiving a bone marrow transplantation. A nationwide consensus should be achieved among pediatric intensivists and oncologists regarding the threshold clinical conditions requiring Intensive Care Unit (ICU) admission as well as specific critical care protocols. As demonstrated for the critically ill non-oncologic child, it appears unreasonable that pediatric patients with malignancy can be admitted to an adult Intensive Care Unit ICU. On a national basis a pool of refecence institutions should be identified and early referral to an oncologic PICU is warranted

What are the current indications for noninvasive ventilation in children ?

PURPOSE OF REVIEW: The aims of this paper are to examine the physiological rationale for noninvasive respiratory support (NRS) in children older than 1 month with acute respiratory failure, to review clinical available data and to give some practical recommendations for the safe application of NRS. RECENT FINDINGS: NRS is the delivery of ventilatory support without the need for an invasive airway. Two types of NRS are commonly used in the pediatric population: noninvasive continuous positive airway pressure and noninvasive positive pressure ventilation. In general, the evidence to support the use of NRS in children with acute respiratory failure is scarce. However, two randomized studies have been recently published suggesting that noninvasive positive pressure ventilation ameliorates clinical signs and gas exchange while reducing the need for endotracheal intubation. Moreover, noninvasive continuous positive airway pressure and heliox may improve clinical scores and carbon dioxide washout in infants with severe bronchiolitis, without major complications. Data from noncontrolled studies show that NRS unloads the respiratory muscles and that the helmet can be a valid alternative to a facial and/or nasal mask when noninvasive continuous positive airway pressure is administered to children in the early stage of acute respiratory failure. SUMMARY: Preliminary clinical data show that NRS is safe and effective in children with acute respiratory failure

Treatment of acute hypoxemic respiratory failure with continuous positive airway pressure delivered by a new pediatric helmet in comparison with a standard full face mask: A prospective pilot study

OBJECTIVES: To evaluate the feasibility and efficacy of continuous positive airway pressure delivered by a new pediatric helmet in comparison with a standard facial mask in infants with acute hypoxemic respiratory failure. DESIGN: A single-center prospective case-control study. SETTING: Pediatric intensive care unit in a tertiary children hospital. PATIENTS AND INTERVENTIONS: Twenty consecutive infants treated with continuous positive airway pressure by a helmet matched with a control patient treated with continuous positive airway pressure by facial mask and selected by age, weight, PaO2:Fio2, and PaCO2 on pediatric intensive care unit admission. MEASUREMENTS AND MAIN RESULTS: Feasibility was defined as the incidence of continuous positive airway pressure protocol failure secondary to 1) failure to administer continuous positive airway pressure because of intolerance to the interface; 2) deterioration in gas exchange soon after continuous positive airway pressure institution; and 3) major clinical adverse events such as pneumothorax or any hemodynamic instability related to the continuous positive airway pressure safety system device's failure. Evaluation of feasibility included also the total application time of respiratory treatment, the number of continuous positive airway pressure discontinuations/first 24 hrs. Interface-related complications included air leaks, cutaneous pressure sores, eye irritation, inhalation, and gastric distension. The 20 patients and control subjects had similar matching characteristics. Continuous positive airway pressure delivered by a helmet compared with a facial mask reduced continuous positive airway pressure trial failure rate (p = .02), increased application time (p = .001) with less discontinuations (p = .001), and was not associated with an increased rate of major adverse events, resulting in decreased air leaks (p = .04) and pressure sores (p = .002). Both continuous positive airway pressure systems resulted in early and sustained improvement in oxygenation. CONCLUSIONS: The helmet might be considered a viable and safe alternative to a standard facial mask to deliver continuous positive airway pressure in hypoxemic infants in the pediatric intensive care unit setting. In our study, the helmet allowed more prolonged application of continuous positive airway pressure compared with a facial mask, ensuring similar improvement in oxygenation without any adverse events and clinical intolerance

Non-invasive ventilation in pediatric intensive care.

The aims of this paper are: to examine the physiological rationale for noninvasive respiratory support (NRS) in children with acute respiratory failure (ARF); to review clinical available data and to give some practical recommendations to its safe application. NRS is the delivery of ventilatory support without the need of an invasive airway. Two types of NRS are commonly used in the pediatric population: non-invasive continuous positive airway pressure (nCPAP) and non-invasive positive pressure ventilation (nPPV). In general, the evidence to promote the use of NRS in children with ARF is scarce. However, two randomized studies have been recently published suggesting that nPPV ameliorates clinical signs and gas exchange while reducing the need for endotracheal intubation. Moreover, nCPAP and heliox may improve clinical scores and CO2 washout in infants with severe bronchiolitis, without major complications. Data from non controlled studies show that NRS unloads the respiratory muscles and that the helmet can be a valid alternative to facial and/or nasal mask when nCPAP is administered to children in the early stage of ARF

Respiratory mechanics and lung stress/strain in children with acute respiratory distress syndrome

Background: In sedated and paralyzed children with acute respiratory failure, the compliance of respiratory system and functional residual capacity were significantly reduced compared with healthy subjects. However, no major studies in children with ARDS have investigated the role of different levels of PEEP and tidal volume on the partitioned respiratory mechanic (lung and chest wall), stress (transpulmonary pressure) and strain (inflated volume above the functional residual capacity). Methods: The end-expiratory lung volume was measured using a simplified closed circuit helium dilution method. During an inspiratory and expiratory pause, the airway and esophageal pressure were measured. Transpulmonary pressure was computed as the difference between airway and esophageal pressure. Results: Ten intubated sedated paralyzed healthy children and ten children with ARDS underwent a PEEP trial (4 and 12 cmH2O) with a tidal volume of 8, 10 and 12\ua0ml/kgIBW. The two groups were comparable for age and BMI (2.5 [1.0\u20135.5] vs 3.0 [1.7\u20137.2] years and 15.1\ua0\ub1\ua02.4 vs 15.3\ua0\ub1\ua03.0\ua0kg/m2). The functional residual capacity in ARDS patients was significantly lower as compared to the control group (10.4 [9.1\u201314.3] vs 16.6 [11.7\u201324.6] ml/kg, p\ua0=\ua00.04). The ARDS patients had a significantly lower respiratory system and lung compliance as compared to control subjects (9.9\ua0\ub1\ua05.0 vs 17.8\ua0\ub1\ua06.5, 9.3\ua0\ub1\ua04.9 vs 16.9\ua0\ub1\ua04.1 at 4 cmH2O of PEEP and 11.7\ua0\ub1\ua05.8 vs 23.7\ua0\ub1\ua06.8, 10.0\ua0\ub1\ua04.9 vs 23.4\ua0\ub1\ua07.5 at 12 cmH2O of PEEP). The compliance of the chest wall was similar in both groups (76.7\ua0\ub1\ua030.2 vs 94.4\ua0\ub1\ua076.4 and 92.6\ua0\ub1\ua065.3 vs 90.0\ua0\ub1\ua061.7 at 4 and 12 cmH2O of PEEP). The lung stress and strain were significantly higher in ARDS patients as compared to control subjects and were poorly related to airway pressure and tidal volume normalized for body weight. Conclusions: Airway pressures and tidal volume normalized to body weight are poor surrogates for lung stress and strain in mild pediatric ARDS. Trial registration: Clinialtrials.gov NCT02036801. Registered 13 January 201