Showing papers by "Giorgio Conti published in 2021"

Effect of Helmet Noninvasive Ventilation vs High-Flow Nasal Oxygen on Days Free of Respiratory Support in Patients With COVID-19 and Moderate to Severe Hypoxemic Respiratory Failure: The HENIVOT Randomized Clinical Trial.

Abstract: Importance High-flow nasal oxygen is recommended as initial treatment for acute hypoxemic respiratory failure and is widely applied in patients with COVID-19. Objective To assess whether helmet noninvasive ventilation can increase the days free of respiratory support in patients with COVID-19 compared with high-flow nasal oxygen alone. Design, Setting, and Participants Multicenter randomized clinical trial in 4 intensive care units (ICUs) in Italy between October and December 2020, end of follow-up February 11, 2021, including 109 patients with COVID-19 and moderate to severe hypoxemic respiratory failure (ratio of partial pressure of arterial oxygen to fraction of inspired oxygen ≤200). Interventions Participants were randomly assigned to receive continuous treatment with helmet noninvasive ventilation (positive end-expiratory pressure, 10-12 cm H2O; pressure support, 10-12 cm H2O) for at least 48 hours eventually followed by high-flow nasal oxygen (n = 54) or high-flow oxygen alone (60 L/min) (n = 55). Main Outcomes and Measures The primary outcome was the number of days free of respiratory support within 28 days after enrollment. Secondary outcomes included the proportion of patients who required endotracheal intubation within 28 days from study enrollment, the number of days free of invasive mechanical ventilation at day 28, the number of days free of invasive mechanical ventilation at day 60, in-ICU mortality, in-hospital mortality, 28-day mortality, 60-day mortality, ICU length of stay, and hospital length of stay. Results Among 110 patients who were randomized, 109 (99%) completed the trial (median age, 65 years [interquartile range {IQR}, 55-70]; 21 women [19%]). The median days free of respiratory support within 28 days after randomization were 20 (IQR, 0-25) in the helmet group and 18 (IQR, 0-22) in the high-flow nasal oxygen group, a difference that was not statistically significant (mean difference, 2 days [95% CI, −2 to 6];P = .26). Of 9 prespecified secondary outcomes reported, 7 showed no significant difference. The rate of endotracheal intubation was significantly lower in the helmet group than in the high-flow nasal oxygen group (30% vs 51%; difference, −21% [95% CI, −38% to −3%];P = .03). The median number of days free of invasive mechanical ventilation within 28 days was significantly higher in the helmet group than in the high-flow nasal oxygen group (28 [IQR, 13-28] vs 25 [IQR 4-28]; mean difference, 3 days [95% CI, 0-7];P = .04). The rate of in-hospital mortality was 24% in the helmet group and 25% in the high-flow nasal oxygen group (absolute difference, −1% [95% CI, −17% to 15%];P > .99). Conclusions and Relevance Among patients with COVID-19 and moderate to severe hypoxemia, treatment with helmet noninvasive ventilation, compared with high-flow nasal oxygen, resulted in no significant difference in the number of days free of respiratory support within 28 days. Further research is warranted to determine effects on other outcomes, including the need for endotracheal intubation. Trial Registration ClinicalTrials.gov Identifier:NCT04502576

Surfactant therapies for pediatric and neonatal ARDS: ESPNIC expert consensus opinion for future research steps

Abstract: Pediatric (PARDS) and neonatal (NARDS) acute respiratory distress syndrome have different age-specific characteristics and definitions. Trials on surfactant for ARDS in children and neonates have been performed well before the PARDS and NARDS definitions and yielded conflicting results. This is mainly due to heterogeneity in study design reflecting historic lack of pathobiology knowledge. We reviewed the available clinical and preclinical data to create an expert consensus aiming to inform future research steps and advance the knowledge in this area. Eight trials investigated the use of surfactant for ARDS in children and ten in neonates, respectively. There were improvements in oxygenation (7/8 trials in children, 7/10 in neonates) and mortality (3/8 trials in children, 1/10 in neonates) improved. Trials were heterogeneous for patients’ characteristics, surfactant type and administration strategy. Key pathobiological concepts were missed in study design. Consensus with strong agreement was reached on four statements: We advocate for further well-designed preclinical and clinical studies to investigate the use of surfactant for PARDS and NARDS following these principles.

Diaphragm thickening fraction predicts noninvasive ventilation outcome: a preliminary physiological study.

Abstract: A correlation between unsuccessful noninvasive ventilation (NIV) and poor outcome has been suggested in de-novo Acute Respiratory Failure (ARF) patients. Consequently, it is of paramount importance to identify accurate predictors of NIV outcome. The aim of our preliminary study is to evaluate the Diaphragmatic Thickening Fraction (DTF) and the respiratory rate/DTF ratio as predictors of NIV outcome in de-novo ARF patients. Over 36 months, we studied patients admitted to the emergency department with a diagnosis of de-novo ARF and requiring NIV treatment. DTF and respiratory rate/DTF ratio were measured by 2 trained operators at baseline, at 1, 4, 12, 24, 48, 72 and 96 h of NIV treatment and/or until NIV discontinuation or intubation. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the ability of DTF and respiratory rate/DTF ratio to distinguish between patients who were successfully weaned and those who failed. Eighteen patients were included. We found overall good repeatability of DTF assessment, with Intra-class Correlation Coefficient (ICC) of 0.82 (95% confidence interval 0.72–0.88). The cut-off values of DTF for prediction of NIV failure were 0.6 for both operators (p < 0.0001). DTF and respiratory rate/DTF ratio may both represent valid, feasible and noninvasive tools to predict NIV outcome in patients with de-novo ARF. Trial registration ClinicalTrials.gov Identifier: NCT02976233, registered 26 November 2016.

Intranasal Delivery of Nerve Growth Factor in Neurodegenerative Diseases and Neurotrauma

Abstract: Since the 1980s, the development of a pharmacology based on nerve growth factor (NGF) has been postulated for the therapy of Alzheimer's disease (AD). This hypothesis was based on the rescuing effect of the neurotrophin on the cholinergic phenotype of the basal forebrain neurons, primarily compromised during the development of AD. Subsequently, the use of NGF was put forward to treat a broader spectrum of neurological conditions affecting the central nervous system, such as Parkinson's disease, degenerative retinopathies, severe brain traumas and neurodevelopmental dysfunctions. While supported by solid rational assumptions, the progress of a pharmacology founded on these hypotheses has been hampered by the difficulty of conveying NGF towards the brain parenchyma without resorting to invasive and risky delivery methods. At the end of the last century, it was shown that NGF administered intranasally to the olfactory epithelium was able to spread into the brain parenchyma. Notably, after such delivery, pharmacologically relevant concentration of exogenous NGF was found in brain areas located at considerable distances from the injection site along the rostral-caudal axis. These observations paved the way for preclinical characterization and clinical trials on the efficacy of intranasal NGF for the treatment of neurodegenerative diseases and of the consequences of brain trauma. In this review, a summary of the preclinical and clinical studies published to date will be attempted, as well as a discussion about the mechanisms underlying the efficacy and the possible development of the pharmacology based on intranasal conveyance of NGF to the brain

Comparison between sedation room and operating room in central venous catheter positioning in children

Abstract: Background:Placement of central venous access devices is a clinical procedure associated with some risk of adverse events and with a relevant cost Careful choice of the device, appropriate inserti

Perioperative management of children with neuromuscular disorders based on a common protocol: A prospective, national study in Italy.

Abstract: Background Children with neuromuscular diseases (NMDs) often display respiratory muscle weakness which increases the risk of postoperative pulmonary complications (PPCs) after general anaesthesia. Non-invasive ventilation (NIV) associated with mechanical insufflation-exsufflation (MI-E) can reduce the incidence and severity of PPCs. The aim of this study was to report our experience with a shared perioperative protocol that consists in using NIV combined with MI-E to improve the postoperative outcome of NMD children (IT-NEUMA-Ped). Method We conducted a multicentre, observational study on 167 consecutive paediatric patients with NMDs undergoing anaesthesia from December 2015 to December 2018 in a network of 13 Italian hospitals. Results We found that 89% of the 167 children (mean age 8 years old) were at high risk of PPCs, due to the presence of at least one respiratory risk factor. In particular, 51% of them had preoperative ventilatory support dependence. Only 14 (8%) patients developed PPCs, and only two patients needed tracheostomy. Average hospital length of stay (LOS) was 6 (2-14) days. The study population was stratified according to preoperative respiratory devices dependency and invasiveness of the procedure. Patients with preoperative ventilatory support dependence showed significantly higher intensive care unit (ICU) admission rate and longer hospital LOS. Conclusion Disease severity seems to be more related to the outcome of this population than invasiveness of procedures. NIV combined with MI-E can help in preventing and resolve PPCs.

The management of pediatric severe traumatic brain injury: Italian Guidelines.

Abstract: Introduction The aim of the work was to update the "Guidelines for the Management of Severe Traumatic Brain Injury" published in 2012, to reflect the new available evidence, and develop the Italian national guideline for the management of severe pediatric head injuries to reduce variation in practice and ensure optimal care to patients. Evidence acquisition MEDLINE and EMBASE were searched from January 2009 to October 2017. Inclusion criteria were English language, pediatric populations (0-18 years) or mixed populations (pediatric/adult) with available age subgroup analyses. The guideline development process was started by the Promoting Group that composed a multidisciplinary panel of experts, with the representatives of the Scientific Societies, the independent expert specialists and a representative of the Patient Associations. The panel selected the clinical questions, discussed the evidence and formulated the text of the recommendations. The documentarists of the University of Florence oversaw the bibliographic research strategy. A group of literature reviewers evaluated the selected literature and compiled the table of evidence for each clinical question. Evidence synthesis The search strategies identified 4254 articles. We selected 3227 abstract (first screening) and, finally included 67 articles (second screening) to update the guideline. This Italian update includes 25 evidence-based recommendations and 5 research recommendations. Conclusions In recent years, progress has been made on the understanding of severe pediatric brain injury, as well as on that concerning all major traumatic pathology. This has led to a progressive improvement in the clinical outcome, although the quantity and quality of evidence remains particularly low.

Implementation of noninvasive neurally adjusted ventilatory assist in pediatric acute respiratory failure: a controlled before-after quality improvement study

Abstract: Pediatric noninvasive neurally adjusted ventilatory assist (NIV-NAVA) has been shown to improve patient-ventilator interaction but no data on clinical outcomes are available. Aim of this study was to compare NIV-NAVA with noninvasive pressure support (NIV-PS) in children with acute hypoxemic respiratory failure (AHRF), in a single-center before-after study. A cohort of thirty-four NIV-PS patients (before group) admitted to our PICU within the 2 years prior NAVA introduction was compared with a cohort of thirty children treated with NIV-NAVA during implementation phase (after group). The primary end-point was intubation rate between groups. Days on mechanical ventilation, number of invasive devices, nosocomial infections, PICU/hospital length of stay (LOS), and physiological parameters at 2 and 24 h after admission were considered. Intubation rate was lower in the NIV-NAVA group as compared to the NIV-PS group (p = 0.006). Patients treated with NIV-NAVA required fewer invasive devices (p = 0.032) and had lower incidence of ventilator-acquired pneumonia (p = 0.004) and shorter PICU (p = 0.032) and hospital LOS (p = 0.013). At 2 h, NIV-NAVA compared with NIV-PS resulted in higher paO2:FIO2 (p = 0.017), lower paCO2 (p = 0.002), RR (p = 0.026), and HR (p = 0.009). Early NIV-NAVA vs NIV-PS was associated to lower intubation rate and shorter PICU and hospital LOS. Further studies are needed in order to confirm these preliminary data.

Should high-flow through nasal cannula be used during bronchoscopy in critically ill patients with hypoxemic acute respiratory failure?

Abstract: Flexible fiberoptic bronchoscopy (FOB) is an invasive procedure with diagnostic and/or therapeutic purposes commonly used in critically ill patients. FOB may be complicated by desaturation, onset or worsening of the respiratory failure, and hemodynamic instability due to cardio-respiratory alterations occurring during the procedure. Increasing evidences suggest the use of high-flow through nasal cannula (HFNC) over conventional oxygen therapy (COT) in critically ill patients with acute respiratory failure (ARF). Indeed, HFNC has a rationale and possible physiologic advantages, even during FOB. However, to date, evidences in favor of HFNC over COT or continuous positive airway pressure (CPAP) or non-invasive ventilation (NIV) during FOB are still weak. Nonetheless, in critically ill patients with hypoxemic ARF, the choice of the oxygenation strategy during a FOB is challenging. Based on a review of the literature, HFNC may be preferred over COT in patients with mild to moderate hypoxemic ARF, without cardiac failure or hemodynamic instability. On the opposite, in critically ill patients with more severe hypoxemic ARF or in the presence of cardiac failure or hemodynamic instability, CPAP or NIV, applied with specifically designed interfaces, may be preferred over HFNC.

Neonatal Life-Threatening Nonoliguric Hyperkalemia Under Therapeutic Hypothermia.

Abstract: To illustrate our experience with two cases of neonatal life-threatening hyperkalemia during therapeutic hypothermia (TH) despite a normal acid-base status, urine output, and preserved renal function. Clinical cases are presented from Pediatric Intensive Care Unit (PICU) admission to the onset of the hyperkalemia, with related complications and after resolution. Similar cases were not retrieved from a critical review of pertinent literature. Severe hyperkalemia pathophysiology and risk factors have been debated. Two full-term adequate for weight female neonates were admitted to PICU because of perinatal asphyxia who underwent TH. Prenatal history was completely uneventful, nor hereditary genetic conditions were reported; moreover, long-term follow-up ruled out any metabolic or renal disease. Despite an accurate evaluation of previous clinical series and literature on TH and perinatal asphyxia, these hyperkalemic episodes remain unexplained. The hypoxic-ischemic insult may affect multiple organs, mainly central nervous system, heart, lung, and kidneys; acute muscle breakdown and consequent rising of myoglobin may also have a precipitating role in acute kidney failure (AKF) and hyperkalemia. Electrolyte imbalance is a possible finding as a consequence of combined cell injury and AKF. In contrast, an isolated severe hyperkalemia is exceedingly rare in nonoliguric neonates.

Noninvasive Ventilation in a Pediatric Trauma Center: A Cohort Study

Abstract: Objective:To determine whether non-invasive ventilation (NIV) can avoid the need for tracheal intubation and/or reduce the duration of invasive ventilation (IMV) in previously intubated patients ad...