Effectiveness of a Novel Tablet Application in Reducing Guideline Deviations During Pediatric Cardiac Arrest: A Randomized Clinical Trial.

Importance: Deviations from international resuscitation guidelines during the management of pediatric cardiac arrest are frequent and affect clinical outcomes. An interactive tablet application (app), PediAppRREST, was developed to reduce guideline deviations during pediatric cardiac arrest. Objective: To assess the effectiveness of PediAppRREST in improving the management of simulated in-hospital pediatric cardiac arrest. Design, Setting, and Participants: This multicenter 3-group simulation-based randomized clinical trial was conducted from September 2020 to December 2021 at 4 Italian university hospitals (Padua, Florence, Rome, Novara). Participants included residents in pediatrics, emergency medicine, and anesthesiology. Analyses were conducted as intention-to-treat. Data were analyzed from January to June 2022. Interventions: Teams were randomized to 1 of 3 study groups: an intervention group that used the PediAppRREST app; a control group that used a paper-based cognitive aid, the Pediatric Advanced Life Support (PALS) pocket card; and a control group that used no cognitive aids. All the teams managed the same standardized simulated scenario of nonshockable pediatric cardiac arrest. Main Outcomes and Measures: The primary outcome was the number of deviations from guidelines, measured by a 15-item checklist based on guideline recommendations. The main secondary outcomes were quality of chest compressions, team clinical performance (measured by the Clinical Performance Tool), and perceived team leader's workload. Study outcomes were assessed via video reviews of the scenarios. Results: Overall 100 teams of 300 participants (mean [SD] age, 29.0 [2.2] years; 195 [65%] female) were analyzed by intention-to-treat, including 32 teams randomized to the PediAppRREST group, 35 teams randomized to the PALS control group, and 33 teams randomized to the null control group. Participant characteristics (210 pediatric residents [70%]; 48 anesthesiology residents [16%]; 42 emergency medicine residents [14%]) were not statistically different among the study groups. The number of deviations from guidelines was significantly lower in the PediAppRREST group than in the control groups (mean difference vs PALS control, -3.0; 95% CI, -4.0 to -1.9; P < .001; mean difference vs null control, -2.6; 95% CI, -3.6 to -1.5; P < .001). Clinical Performance Tool scores were significantly higher in the PediAppRREST group than control groups (mean difference vs PALS control, 1.4; 95% CI, 0.4 to 2.3; P = .002; mean difference vs null control, 1.1; 95% CI, 0.2 to 2.1; P = .01). The other secondary outcomes did not significantly differ among the study groups. Conclusions and Relevance: In this randomized clinical trial, the use of the PediAppRREST app resulted in fewer deviations from guidelines and a better team clinical performance during the management of pediatric cardiac arrest. Trial Registration: ClinicalTrials.gov Identifier: NCT04619498.

Pediatric basic course goes virtual: transition from face to face to hybrid learning in pediatric critical care.

BACKGROUND: To explore the impact of the transition from a traditional face-to-face course delivering essential contents in pediatric critical care to a hybrid format consisting of an online pre-course self-directed learning, an online facilitated discussion, and a face-to-face edition. METHODS: Attendees and faculty were surveyed after the face-to-face course and the hybrid version to evaluate the effectiveness and satisfaction of participants with the course. RESULTS: Fifty-seven students attended multiple formats of the Pediatric Basic Course between January 2020 and October 2021 in Udine, Italy. We compared course evaluation data from the 29 attendees of the face-to-face course with the 28 of the hybrid edition. Data collected included participant demographics, participant self-assessed pre and post-course ''confidence'' with a range of pediatric intensive care-related activities, and their satisfaction with elements of the course. There were no statistical differences in participant demographics or pre and post-course confidence scores. Overall satisfaction with the face-to-face course was marginally higher, 4.59 vs. 4.25/5, but did not reach significance. Pre-recorded lectures which could be viewed several times, were highlighted as a positive for the hybrid course. Residents found no significant differences comparing the two courses in rating the lectures and the technical skills stations. Hybrid course facilities (online platform and uploaded material) were reported to be clear, accessible, and valuable by 87% of attendees. After six months, they still find the course relevant to their clinical practice (75%). Candidates considered the respiratory failure and mechanical ventilation modules the most relevant modules. CONCLUSIONS: The Pediatric Basic Course helps residents strengthen their learning and identify areas to improve their knowledge. Both face-to-face and hybrid model versions of the course improved attendees' knowledge and perceived confidence in managing the critically ill child.

PediAppRREST: effectiveness of an interactive cognitive support tablet app in reducing deviations from guidelines in the management of paediatric cardiac arrest: protocol for a simulation-based randomised controlled trial.

INTRODUCTION: Paediatric cardiac arrest (PCA), despite its low incidence, has a high mortality. Its management is complex and deviations from guideline recommendations occur frequently. We developed a new interactive tablet app, named PediAppRREST, to support the management of PCA. The app received a good usability evaluation in a previous pilot trial. The aim of the study is to evaluate the effectiveness of the PediAppRREST app in reducing deviations from guideline recommendations in PCA management. METHODS AND ANALYSIS: This is a multicentre, simulation-based, randomised controlled, three-parallel-arm study. Participants are residents in Paediatric, Emergency Medicine, and Anaesthesiology programmes in Italy. All 105 teams (315 participants) manage the same scenario of in-hospital PCA. Teams are randomised by the study statistician into one of three study arms for the management of the PCA scenario: (1) an intervention group using the PediAppRREST app or (2) a control group Paediatric Advanced Life Support (CtrlPALS+) using the PALS pocket reference card; or (3) a control group (CtrlPALS-) not allowed to use any PALS-related cognitive aid. The primary outcome of the study is the number of deviations (delays and errors) in PCA management from PALS guideline recommendations, according to a novel checklist, named c-DEV15plus. The c-DEV15plus scores will be compared between groups with a one-way analysis of variance model, followed by the Tukey-Kramer multiple comparisons adjustment procedure in case of statistical significance. ETHICS AND DISSEMINATION: The Ethics Committee of the University Hospital of Padova, coordinating centre of the trial, deemed the project to be a negligible risk study and approved it through an expedited review process. The results of the study will be disseminated in peer-reviewed journals, and at national and international scientific conferences. Based on the study results, the PediAppRREST app will be further refined and will be available for download by institutions/healthcare professionals. TRIAL REGISTRATION NUMBER: NCT04619498; Pre-results.

Influence of summer tourist flows on occurrence of out-of-hospital cardiac arrest in an Italian tourist-intensive area.

INTRODUCTION: The study aims to evaluate the seasonal variation of out-of hospital cardiac arrest (OHCA) in a tourist-intensive area. METHODS: Data of all OHCA treated by the Emergency Medical Service of Lecce (LE-EMS), Italy, between 2013 and 2017, were retrospectively analyzed and complemented with information about tourist flows, in order to determine the influence of the seasonal variation of population on incidence and outcome. RESULTS: Tourist arrivals were around 1,700,000 per year, mostly in summer, adding up to 803,161 residents. The occurrence of OHCA did not show a monthly variation when referring to the resident population (p = 0.90). When taking into account the tourist flows, a difference in occurrence of OHCA across months was found, with the highest rate of arrests in December and the lowest in August (10.3 vs 3.4 per 100,000 persons, p < 0.01). No difference was found in terms of EMS arrival time and event survival rate between summer and the rest of the year (13.6 vs 13.8 min, p = 0.55, and 4.4% vs 4.5%, p = 0.86, respectively). CONCLUSION: In summer tourism areas, the occurrence of OHCA is unchanged throughout the year, while the actual population presents seasonal increases. Summer enhancement of provincial EMS may contribute to maintain the performance of emergency care.

Missense variant in TPI1 (Arg189Gln) causes neurologic deficits through structural changes in the triosephosphate isomerase catalytic site and reduced enzyme levels in vivo.

Mutations in the gene triosephosphate isomerase (TPI) lead to a severe multisystem condition that is characterized by hemolytic anemia, a weakened immune system, and significant neurologic symptoms such as seizures, distal neuropathy, and intellectual disability. No effective therapy is available. Here we report a compound heterozygous patient with a novel TPI pathogenic variant (NM_000365.5:c.569G>A:p.(Arg189Gln)) in combination with the common (NM_000365.5:c.315G>C:p.(Glu104Asp)) allele. We characterized the novel variant by mutating the homologous Arg in Drosophila using a genomic engineering system, demonstrating that missense mutations at this position cause a strong loss of function. Compound heterozygote animals were generated and exhibit motor behavioural deficits and markedly reduced protein levels. Furthermore, examinations of the TPIArg189Gln/TPIGlu104Asp patient fibroblasts confirmed the reduction of TPI levels, suggesting that Arg189Gln may also affect the stability of the protein. The Arg189 residue participates in two salt bridges on the backside of the TPI enzyme dimer, and we reveal that a mutation at this position alters the coordination of the substrate-binding site and important catalytic residues. Collectively, these data reveal a new human pathogenic variant associated with TPI deficiency, identify the Arg189 salt bridge as critical for organizing the catalytic site of the TPI enzyme, and demonstrates that reduced TPI levels are associated with human TPI deficiency. These findings advance our understanding of the molecular pathogenesis of the disease, and suggest new therapeutic avenues for pre-clinical trials.

Weaning of Children With Burn Injury by Noninvasive Ventilation: A Clinical Experience.

The aim of this study was to report the respiratory management of a cohort of infants admitted to a Pediatric Intensive Care Unit (PICU) over a 7-year period due to severe burn injury and the potential benefits of noninvasive ventilation (NIV). A retrospective review of all pediatric patients admitted to PICU between 2009 and 2016 was conducted. From 2009 to 2016, 118 infants and children with burn injury were admitted to our institution (median age 16 months [IQR = 12.2-20]); 51.7% of them had face burns, 37.3% underwent tracheal intubation, and 30.5% had a PICU stay greater than 7 days. Ventilated patients had a longer PICU stay (13 days [IQR = 8-26] vs 4.5 days [IQR = 2-13]). Both ventilation requirement and TBSA% correlated with PICU stay (r = .955, p < .0001 and r = .335, p = .002, respectively), while ventilation was best related in those >1 week (r = .964, p < .0001 for ventilation, and r = -.079, p = .680, for TBSA%). NIV was introduced in 10 patients, with the aim of shorten the invasive ventilation requirement. As evidenced in our work, mechanical ventilation is frequently needed in burned children admitted to PICU and it is one of the main factors influencing PICU length of stay. No difference was found in terms of PICU length of stay and invasive mechanical ventilation time between children who underwent NIV and children who did not, despite children who underwent NIV had a larger burn surface. NIV can possibly shorten the total invasive ventilation time and related complications.

Comparative bench study evaluation of different infant interfaces for non-invasive ventilation.

BACKGROUND: To compare, in terms of patient-ventilator interaction and performance, a new nasal mask (Respireo, AirLiquide, FR) with the Endotracheal tube (ET) and a commonly used nasal mask (FPM, Fisher and Paykel, NZ) for delivering Pressure Support Ventilation (PSV) in an infant model of Acute Respiratory Failure (ARF). METHODS: An active test lung (ASL 5000) connected to an infant mannequin through 3 different interfaces (Respireo, ET and FPM), was ventilated with a standard ICU ventilator set in PSV. The test lung was set to simulate a 5.5 kg infant with ARF, breathing at 50 and 60 breaths/min). Non-invasive ventilation (NIV) mode was not used and the leaks were nearly zero. RESULTS: The ET showed the shortest inspiratory trigger delay and pressurization time compared to FPM and Respireo (p < 0.01). At each respiratory rate tested, the FPM showed the shortest Expiratory trigger delay compared to ET and Respireo (p < 0.01). The Respireo presented a lower value of Inspiratory pressure-time product and trigger pressure drop than ET (p < 0.01), while no significant difference was found in terms of pressure-time product at 300 and 500 ms. During all tests, compared with the FPM, ET showed a significantly higher tidal volume (VT) delivered (p < 0.01), while Respireo showed a trend toward an increase of tidal volume delivered compared with FPM. CONCLUSIONS: The ET showed a better patient-ventilator interaction and performance compared to both the nasal masks. Despite the higher internal volume, Respireo showed a trend toward an increase of the delivered tidal volume; globally, its efficiency in terms of patient-ventilator interaction was comparable to the FPM, which is the infant NIV mask characterized by the smaller internal volume among the (few) models on the market.

Interleukin-6 and nerve growth factor upregulation correlates with improved outcome in children with severe traumatic brain injury.

Secondary brain damage after traumatic brain injury (TBI) involves neuro-inflammatory mechanisms that are mainly dependent on the intracerebral production of cytokines. Interleukin-6 (IL-6) may have a role both in the pathogenesis of neuronal damage and in the recovery mechanisms of injured neurons through the modulation of nerve growth factor (NGF) biosynthesis. However, the relationship between IL-6 and NGF expression and the severity and outcome of TBI remains controversial. We have conducted a prospective observational clinical study to determine whether the concentration of IL-6 and NGF in the cerebrospinal fluid (CSF) of children with TBI correlates with the severity of the injury and neurologic outcome of patients. CSF samples were collected from 29 children at 2 h (time T1) and 48 h (time T2) after severe TBI, and from 31 matched controls. TBI severity was evaluated by Glasgow Coma Scale (GCS) and neurologic outcome by Glasgow Outcome Score (GOS). CSF concentrations of IL-6 and NGF were measured by immunoenzymatic assays. Early NGF concentrations (T1) correlated significantly with head injury severity, whereas no correlation was found between GCS and IL-6. Furthermore, IL-6 and NGF upregulation after injury was associated with better neurologic outcomes. Based on these findings, we posit that NGF expression is a useful marker of brain damage following severe TBI. Moreover, the early upregulation of both IL-6 and NGF, which correlates with a favorable neurologic outcome, may reflect an endogenous attempt at neuroprotection in response to the damaging biochemical and molecular cascades triggered by traumatic insult.

Patient-controlled analgesia with fentanil and midazolam in children with postoperative neurosurgical pain.

BACKGROUND: Pain is the most common discomfort experienced by children undergoing major operations. It is most often not adequately treated because of inexperience and unfounded fears related to the use of opioid drugs. In adults, patient-controlled analgesia (PCA) is widely administered, while in children, its use with opioid drugs is still under evaluation for safety and efficacy. OBJECTIVES: The objective of the study is to evaluate the safety and efficacy of an opioid drug (fentanil) administered by PCA associated with a sedative-adjuvant drug (midazolam) administered by continuous infusion in children having undergone major neurosurgical procedures. MATERIALS AND METHODS: Sixteen children with moderate to severe postoperative pain were treated with fentanil by PCA (booster doses of 1 microg/kg) plus continuous infusion of midazolam (2 microg/kg per min) by an intravenous route. To evaluate safety and efficacy of this analgesic protocol, different subjective and objective parameters were monitored at 4-h intervals. In addition, patients' satisfaction was assessed by a questionnaire at the end of the treatment. MAIN RESULTS: All children experienced a good degree of analgesia and did not require any other analgesic drug during the treatment. Both subjective and objective parameters improved after starting pain-relieving treatment, and no major side effects occurred. The analysis of the answers of the questionnaire administered to the children showed a high grade of satisfaction. CONCLUSIONS: PCA with fentanil plus continuous infusion of midazolam is a safe and efficacious method for analgesia in children with moderate to severe postoperative neurosurgical pain. The association of midazolam to fentanil also contributes to control anxiety and stress in this subset of patients and does not show any important side effects.

Nerve growth factor expression correlates with severity and outcome of traumatic brain injury in children.

BACKGROUND: Secondary brain damage after traumatic brain injury (TBI) involves neuro-inflammatory mechanisms, mainly dependent on the intracerebral production of cytokines. In particular, interleukin 1beta (IL-1beta) is associated with neuronal damage, while interleukin 6 (IL-6) exerts a neuroprotective role due to its ability to modulate neurotrophins biosynthesis. However, the relationship between these cytokines and neurotrophins with the severity and outcome of TBI remains still controversial. AIMS: To determine whether the concentration of IL-1beta and IL-6 and neurotrophins (nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF)) in the cerebrospinal fluid (CSF) of children with TBI correlates with the severity of the injury and its neurologic outcome. METHODS: Prospective observational clinical study in a university hospital. CSF samples were collected from 27 children at 2h (Time T1) and 48 h (Time T2) after severe TBI, and from 21 matched controls. Severity of TBI was evaluated by GCS and neurologic outcome by GOS. CSF concentrations of cytokines and neurotrophins were measured by immunoenzymatic assays. RESULTS: Early NGF and IL-1beta concentrations (T1) correlated significantly with the severity of head injury, whereas no correlation was found for IL-6, BDNF, and GDNF. Furthermore, higher NGF and IL-6 and lower IL-1beta expression at T2 were associated with better neurologic outcomes. No significant association was found between BDNF or GDNF expression and neurologic outcome. CONCLUSIONS: NGF concentration in CSF is a useful marker of brain damage following severe TBI and its up-regulation, in the first 48 h after head injury together with lower IL-1beta expression, correlates with a favorable neurologic outcome. Clinical and prognostic information may also be obtained from IL-6 expression.

Sharing features of uncommon respiratory syncytial virus complications in infants.

We describe 4 nonconsecutive cases of infants admitted to Catholic University pediatric intensive care unit (PICU) because of complicated respiratory syncytial virus (RSV) infection during winter RSV outbreaks from the year 2000 to the year 2003. A hyponatremic epileptic status (as in the first case) has been reported by several authors as a rare RSV complication, potentially leading to death. The second infant developed a serious pulmonary edema after a subglottic obstruction (croup) associated with RSV infection. The remaining 2 infants developed a pneumothorax and subcutaneous emphysema while breathing spontaneously during an RSV bronchiolitis. In all infants, a full recovery and PICU discharge was achieved despite the need for mechanical ventilation in cases 1 and 2. Increased intrapleural negative pressure or its combination with hypoxia/hypercapnia has been suggested as the common factor possibly joining these different clinical pictures.

Neurotrophin overexpression in lower airways of infants with respiratory syncytial virus infection.

RATIONALE: Nerve growth factor and its receptors are upregulated in the lungs of weanling rats with lower respiratory tract infection caused by the respiratory syncytial virus (RSV), and this is a major mechanism of the inflammatory response against the virus. However, no information is available in humans. OBJECTIVES: We sought to determine whether the expression of neurotrophic factors and receptors is increased in human infants infected with RSV. METHODS: We used a highly sensitive immunoassay to measure the concentrations of nerve growth factor and brain-derived neurotrophic factor proteins in serum samples and in the supernatants and cell fractions of nonbronchoscopic bronchoalveolar lavage fluid. We also used immunofluorescence to detect expression in airway cells of the tyrosine kinase receptor TrkA, which binds nerve growth factor with high affinity. Samples were obtained at 24 and 48 hours postintubation from 31 mechanically ventilated infants: 15 patients with RSV infection, 5 patients with respiratory infection negative for RSV, and 11 postsurgical patients without respiratory infection. MAIN RESULTS: Data show significantly higher concentrations of both neurotrophins in the cell fractions of bronchoalveolar lavage samples obtained from infants with RSV infection compared with control infants, whereas no significant difference was found in supernatants or serum samples. We also detected tyrosine kinase receptor immunoreactivity only in cells from airways infected with RSV. CONCLUSIONS: We conclude that neurotrophic factors and receptors are overexpressed in human airways infected by RSV, and may contribute to airway inflammation and hyperreactivity.

HFOV in premature neonates: effects on pulmonary mechanics and epithelial lining fluid cytokines. A randomized controlled trial.

OBJECTIVE: Ventilation strategies for preterm neonates may influence the severity of pulmonary dysfunction and later development of chronic lung disease. The objective of this report is to compare the effects of high-frequency oscillatory ventilation (HFOV) versus synchronized intermittent mandatory ventilation (sIMV) from the points of views of biochemical and functional variables. DESIGN: Randomized controlled trial. SETTING: Third level NICU. PATIENTS AND PARTICIPANTS: Forty preterm neonates with a gestational age of 24-29 weeks were randomly assigned to one of the two above-mentioned ventilation strategies within 30 min from birth. MEASUREMENTS AND RESULTS: At 1, 3, 5, and 7 days, the babies were monitored by means of ventilator indices, pulmonary function, and eight pro-inflammatory or anti-inflammatory cytokines measured in bronchoalveolar lavage fluid. The neonates assigned to the HFOV procedure benefited from early and sustained improvement in pulmonary mechanics and gas exchange-significantly higher dynamic respiratory compliance values, significantly lower expiratory airway resistance and oxygenation index values-with earlier extubation as compared to the neonates assigned to sIMV treatment, and showed significantly lower transforming growth factor-beta1 concentrations in bronchoalveolar lavage fluid. CONCLUSIONS: The results of this randomized clinical trial support the hypothesis that early and exclusive use of HFOV, combined with optimum volume strategy, has a beneficial effect during the acute phase of lung injury.

Effects of early dexamethasone therapy on pulmonary fibrogenic mediators and respiratory mechanics in preterm infants.

Corticosteroid administration may prevent chronic lung disease in premature newborns, perhaps by modulating the synthesis of various cytokines, including those involved in fibrogenic processes. This study analyses the levels of three fibrogenic cytokines, namely vascular endothelial growth factor, transforming growth factor-beta 1 and basic fibroblast growth factor in tracheobronchial aspirate fluids collected from 20 premature newborns randomly assigned to the early dexamethasone group or to the control group. Furthermore, pulmonary function tests were performed on days 0 and 2 following the start of therapy. The results show that early corticosteroid administration reduces transforming growth factor-beta 1 and basic fibroblast growth factor levels, and abolishes the spontaneous vascular endothelial growth factor increase observed in untreated patients, concomitantly with significant improvement of dynamic lung compliance and shorter duration of the intubation period in the treated group of patients. Significant correlations were observed between the levels of transforming growth factor-beta 1 and vascular endothelial growth factor, indicating that the production of both these cytokines is coordinated. Finally, transforming growth factor-beta 1 ratios (day 2/day 0), representing early variations of the cytokine levels, were significantly different between treated and untreated subjects and correlated with the dynamic lung compliance ratios and the extubation day, suggesting that the downmodulation of some fibrogenic mediators may be involved in the mode of action of dexamethasone.

Multicenter, randomized, controlled study of porcine surfactant in severe respiratory syncytial virus-induced respiratory failure.

OBJECTIVE: Recently, natural exogenous surfactant replacement has been used in experimental models and clinical trials for the treatment of severe respiratory syncytial virus (RSV) disease. The present study was aimed at verifying this hypothesis and confirming the results of our previous pilot study by assessing the effect of surfactant treatment in mechanically ventilated infants with severe RSV-induced respiratory failure. DESIGN: Multicenter, randomized, controlled study. SETTING: Six pediatric intensive care units staffed by full-time intensive care physicians. PATIENTS: A total of 40 infants (20 treated and 20 controls) with RSV-induced respiratory failure requiring conventional mechanical ventilation (CMV) were randomly assigned to either exogenous surfactant (treated group) or conventional treatment (control group) over a 1-yr period. INTERVENTIONS: Fifty milligrams per kilogram of body weight of porcine-derived natural surfactant (Curosurf) was administered. The drug was instilled by means of a syringe attached to a small suction catheter inserted into the endotracheal tube down to its tip, momentarily disconnecting the patient from CMV. Main Outcome Measures: The assessment consisted of the following outcome variables: duration of CMV, length of intensive care unit stay, gas exchange, respiratory mechanics, re-treatment need, complications, and mortality. RESULTS: The two groups were similar with regard to demographics, Pediatric Risk of Mortality scores, and baseline Pao(2)/Fio(2), Paco(2), and ventilator settings. A marked increase in Pao(2)/Fio(2) and decrease in Paco(2) were observed in the treated group after surfactant administration. Hemodynamic parameters remained unchanged throughout the study period. Peak inspiratory pressure and static compliance were similar at baseline in the two groups. A decrease in peak inspiratory pressure and increase in static compliance were observed in the treated group after surfactant administration. Among surfactant-treated patients, 15 received the treatment within 24 hrs of admission, whereas the remainder (five patients) were treated later. Among children who were treated later, three needed an additional dose of surfactant. None of the children treated within 24 hrs needed an additional dose. Duration of CMV and length of stay in the intensive care unit were significantly shorter in the treated group (4.6 +/- 0.8 and 6.4 +/- 0.9 days, respectively) compared with the control group (5.8 +/- 0.7 and 8.2 +/- 1.1 days, respectively) (p <.0001). No relevant complications were observed, and all the infants survived. CONCLUSIONS: Consistent with our previous study and others, this study shows that surfactant therapy improves gas exchange and respiratory mechanics and shortens CMV and intensive care unit stay in infants with severe RSV-induced respiratory failure.