Effects of non-invasive respiratory support in post-operative patients: a systematic review and network meta-analysis.

BACKGROUND: Re-intubation secondary to post-extubation respiratory failure in post-operative patients is associated with increased patient morbidity and mortality. Non-invasive respiratory support (NRS) alternative to conventional oxygen therapy (COT), i.e., high-flow nasal oxygen, continuous positive airway pressure, and non-invasive ventilation (NIV), has been proposed to prevent or treat post-extubation respiratory failure. Aim of the present study is assessing the effects of NRS application, compared to COT, on the re-intubation rate (primary outcome), and time to re-intubation, incidence of nosocomial pneumonia, patient discomfort, intensive care unit (ICU) and hospital length of stay, and mortality (secondary outcomes) in adult patients extubated after surgery. METHODS: A systematic review and network meta-analysis of randomized and non-randomized controlled trials. A search from Medline, Embase, Scopus, Cochrane Central Register of Controlled Trials, and Web of Science from inception until February 2, 2024 was performed. RESULTS: Thirty-three studies (11,292 patients) were included. Among all NRS modalities, only NIV reduced the re-intubation rate, compared to COT (odds ratio 0.49, 95% confidence interval 0.28; 0.87, p = 0.015, I2 = 60.5%, low certainty of evidence). In particular, this effect was observed in patients receiving NIV for treatment, while not for prevention, of post-extubation respiratory failure, and in patients at high, while not low, risk of post-extubation respiratory failure. NIV reduced the rate of nosocomial pneumonia, ICU length of stay, and ICU, hospital, and long-term mortality, while not worsening patient discomfort. CONCLUSIONS: In post-operative patients receiving NRS after extubation, NIV reduced the rate of re-intubation, compared to COT, when used for treatment of post-extubation respiratory failure and in patients at high risk of post-extubation respiratory failure.

Gram-negative bacterial colonizations before bilateral lung transplant. The impact of 'targeted' versus 'standard' surgical prophylaxis.

BACKGROUND: Infections are one of the most common causes of death after lung transplant (LT). However, the benefit of 'targeted' prophylaxis in LT recipients pre-colonized by Gram-negative (GN) bacteria is still unclear. METHODS: All consecutive bilateral LT recipients admitted to the Intensive Care Unit of the University Hospital of Padua (February 2016-2023) were retrospectively screened. Only patients with pre-existing GN bacterial isolations were enrolled and analyzed according to the antimicrobial surgical prophylaxis ('standard' vs. 'targeted' on the preoperative bacterial isolation). RESULTS: One hundred eighty-one LT recipients were screened, 46 enrolled. Twenty-two (48%) recipients were exposed to 'targeted' prophylaxis, while 24 (52%) to 'standard' prophylaxis. Overall prevalence of postoperative multi-drug resistant (MDR) GN bacteria isolation was 65%, with no differences between the two surgical prophylaxis (p = 0.364). Eleven (79%) patients treated with 'standard' prophylaxis and twelve (75%) with 'targeted' therapy reconfirmed the preoperative GN pathogen (p = 0.999). The prevalence of postoperative infections due to MDR GN bacteria was 50%. Of these recipients, 4 belonged to the 'standard' and 11 to the 'targeted' prophylaxis (p = 0.027). CONCLUSIONS: The administration of a 'targeted' prophylaxis in LT pre-colonized recipients seemed not to prevent the occurrence of postoperative MDR GN infections.

Fungal Infections and Colonization after Bilateral Lung Transplant: A Six-Year Single-Center Experience.

Fungal infections (FIs) are one of the leading causes of morbidity and mortality within the first year of lung transplant (LT) in LT recipients (LTRs). Their prompt identification and treatment are crucial for a favorable LTR outcome. The objectives of our study were to assess (i) the FI incidence and colonization during the first year after a bilateral LT, (ii) the risk factors associated with FI and colonization, and (iii) the differences in fungal incidence according to the different prophylactic strategies. All bilateral LTRs admitted to the intensive care unit of Padua University Hospital were retrospectively screened, excluding patients <18 years of age, those who had been re-transplanted, and those who had received ventilation and/or extracorporeal membrane oxygenation before LT. Overall, 157 patients were included. A total of 13 (8%) patients developed FI, and 36 (23%) developed colonization, which was mostly due to Aspergillus spp. We did not identify independent risk factors for FI. Groups of patients receiving different prophylactic strategies reported a similar incidence of both FI and colonization. The incidence of FI and fungal colonization was 8% and 23%, respectively, with no differences between different antifungal prophylaxes or identified predisposing factors. Further studies with larger numbers are needed to confirm our results.

Asymmetrical high-flow nasal cannula performs similarly to standard interface in patients with acute hypoxemic post-extubation respiratory failure: a pilot study.

BACKGROUND: Standard high-flow nasal cannula (HFNC) is a respiratory support device widely used to manage post-extubation hypoxemic acute respiratory failure (hARF) due to greater comfort, oxygenation, alveolar recruitment, humidification, and reduction of dead space, as compared to conventional oxygen therapy. On the contrary, the effects of the new asymmetrical HFNC interface (Optiflow® Duet system (Fisher & Paykel, Healthcare, Auckland, New Zealand) is still under discussion. Our aim is investigating whether the use of asymmetrical HFNC interface presents any relevant difference, compared with the standard configuration, on lung aeration (as assessed by end-expiratory lung impedance (EELI) measured by electrical impedance tomography (EIT)), diaphragm ultrasound thickening fraction (TFdi) and excursion (DE), ventilatory efficiency (estimated by corrected minute ventilation (MV)), gas exchange, dyspnea, and comfort. METHODS: Pilot physiological crossover randomized controlled study enrolling 20 adults admitted to the Intensive Care unit, invasively ventilated for at least 24 h, and developing post-extubation hARF, i.e., PaO2/set FiO2 < 300 mmHg during Venturi mask (VM) within 120 min after extubation. Each HFNC configuration was applied in a randomized 60 min sequence at a flow rate of 60 L/min. RESULTS: Global EELI, TFdi, DE, ventilatory efficiency, gas exchange and dyspnea were not significantly different, while comfort was greater during asymmetrical HFNC support, as compared to standard interface (10 [7-10] and 8 [7-9], p-value 0.044). CONCLUSIONS: In post-extubation hARF, the use of the asymmetrical HFNC, as compared to standard HFNC interface, slightly improved patient comfort without affecting lung aeration, diaphragm activity, ventilatory efficiency, dyspnea and gas exchange. CLINICAL TRIAL NUMBER: ClinicalTrial.gov. REGISTRATION NUMBER: NCT05838326 (01/05/2023). NEW & NOTEWORTHY: The asymmetrical high-flow nasal cannula oxygen therapy (Optiflow® Duet system (Fisher & Paykel, Healthcare, Auckland, New Zealand) provides greater comfort as compared to standard interface; while their performance in term of lung aeration, diaphragm activity, ventilatory efficiency, dyspnea, and gas exchange is similar.

Echocardiographic assessment of pulmonary capillary wedge pressure by E/e' ratio: A systematic review and meta-analysis.

BACKGROUND: The reliability of echocardiographic methods for the assessment of pulmonary capillary wedge pressure (PCWP) is still a matter of debate. Since its first description, the E/e' ratio has been regarded as a suitable method. The aim of this study is to evaluate the evidence of how E/e' effectively estimates PCWP and its diagnostic accuracy for elevated PCWP. METHODS: We systematically searched MEDLINE and Embase databases for studies investigating the agreement between E/e' and PCWP, from inception to July 2022. We limited our research to studies published from 2010 to date. Retrospective studies and studies on non-adult population were excluded. RESULTS: Twenty-eight studies, involving a total of 1964 subjects, were included. The pooled analysis of the studies showed a modest correlation between E/e' and PCWP. The weighted average correlation (r) is 0.43 (95% CI 0.37-0.48). We found no significant differences between reduced and preserved ejection fraction groups. Thirteen studies analysed the diagnostic accuracy of E/e' for elevated PCWP. The AUC of receiver operating characteristic curves for PCWP >15 mmHg was estimated in the interval 0.6-0.91. DISCUSSION: E/e' appears to have a modest correlation with PCWP and an acceptable accuracy for elevated PCWP. (PROSPERO number, CRD42022333462).

Multidrug-resistant organisms in lung transplant: a narrative review.

PURPOSE OF REVIEW: The purpose of this narrative review is presenting the current knowledge of multidrug-resistant (MDR) pathogens in lung transplant recipients, considering both Gram-positive and Gram-negative bacteria. RECENT FINDINGS: Overall prevalence of Gram-negative pathogens has increased remarkably (4.33/1000 recipient-days) in solid organ transplant recipients, while the prevalence of Gram-positive bacteria seems to be decreasing (0.20 cases/100 transplant-years). In lung transplant, the prevalence of postoperative infections due to MDR-GN bacteria has been assessed between 31 and 57%, and the incidence of carbapenem-resistant Enterobacterales is between 0.4 and 20%, with a related mortality up to 70%. MDR Pseudomonas aeruginosa is common in lung transplant recipients with cystic fibrosis and may contribute to bronchiolitis obliterans syndrome. The prevalence of MDR Gram-positive bacteria is around 30% (predominantly Methicillin-resistant Staphylococcus aureus and Coagulase-negative staphylococcus). SUMMARY: Survival after lung transplant, although lower than in other SOT, is increasing and currently at 60% at 5 years. This review highlights the potential clinical and social burden of postoperative infections in lung transplant recipients, and confirmed that a PI due to MDR bacteria negatively affects survival. A prompt diagnosis, prevention and management of these MDR pathogens should remain the cornerstone for higher goals of care.

Sonographic Evaluation of the Endotracheal Tube Position in the Neonatal Population: A Comprehensive Review and Meta-Analysis.

Background: Endotracheal intubation in neonates is challenging and requires a high level of precision, due to narrow and short airways, especially in preterm newborns. The current gold standard for endotracheal tube (ETT) verification is chest X-ray (CXR); however, this method presents some limitations, such as ionizing radiation exposure and delayed in obtaining the radiographic images, that point of care ultrasound (POCUS) could overcome. Primary Objective: To evaluate ultrasound efficacy in determining ETT placement adequacy in preterm and term newborns. Secondary Objective: To compare the time required for ultrasound confirmation vs. time needed for other standard of care methods. Search Methods: A search in Medline, PubMed, Google Scholar and in the Cochrane Central Register of Controlled Trials (CENTRAL) was performed. Our most recent search was conducted in September 2021 including the following keywords: "newborn", "infant", "neonate", "endotracheal intubation", "endotracheal tube", "ultrasonography", "ultrasound". Selection Criteria: We considered randomized and non-randomized controlled trials, prospective, retrospective and cross-sectional studies published after 2012, involving neonatal intensive care unit (NICU) patients needing intubation/intubated infants and evaluating POCUS efficacy and/or accuracy in detecting ETT position vs. a defined gold-standard method. Three review authors independently assessed the studies' quality and extracted data. Main Results: We identified 14 eligible studies including a total of 602 ETT evaluations in NICU or in the delivery room. In about 80% of cases the gold standard for ETT position verification was CXR. Ultrasound was able to identify the presence of ETT in 96.8% of the evaluations, with a pooled POCUS sensitivity of 93.44% (95% CI: 90.4-95.75%) in detecting an appropriately positioned ETT as assessed by CXR. Bedside ultrasound confirmation was also found to be significantly faster compared to obtaining a CXR. Conclusion: POCUS appears to be a fast and effective technique to identify correct endotracheal intubation in newborns. This review could add value and importance to the use of this promising technique.

Refractory symptoms in paediatric palliative care: can ketamine help?

BACKGROUND: One of the main challenges for paediatric palliative care (PPC) is the management of concomitant, different and severe symptoms that frequently affect the quality of life of PPC patients and are often refractory to commonly used pharmacological treatments. Consequently, many efforts are still needed to find the best therapeutic options to handle these refractory conditions. Since the first synthesis of ketamine in the 1960s, its pharmacokinetic and pharmacodynamic properties have been largely investigated and its potential wide range of clinical applications has become clear. However, this molecule still receives poor attention in some areas, including in children and PPC. This narrative review analyses the use of ketamine in children and the potential extension of its applications in PPC in order to provide new options for treatment in the PPC setting. METHODS: Scientific papers published before October 2020 on MEDLINE, EMBASE and the Cochrane Library were considered. The cited references of the selected papers and the authors' personal collections of literature were reviewed. The terms "palliative care", "ketamine", "neuropathic pain", "procedural pain", "status epilepticus", "refractory pain" and "child", adding "age: birth-18 years" on a further filter were used for the search. DISCUSSION: The use of ketamine in PPC should be more widely considered due to its overall favourable safety profile and its efficacy, which are supported by an increasing number of studies, although in settings different from PPC and of mixed quality. Ketamine should be proposed according to a case-by-case evaluation and the specific diagnosis and the dosage and route of administration should be tailored to the specific needs of patients. Furthermore, there is evidence to suggest that ketamine is safe and efficacious in acute pain. These findings can prompt further research on the use of ketamine for the treatment of acute pain in PPC. CONCLUSION: Ketamine could be a suitable option after the failure of conventional drugs in the treatment of different refractory conditions in PPC.

COVID-19 pneumonia in lung transplant recipients: Report of 2 cases.

Coronavirus disease 2019 (COVID-19) has been declared pandemic since March 2020. In Europe, Italy was the first nation affected by this infection. We report anamnestic data, clinical features, and therapeutic management of 2 lung transplant recipients with confirmed COVID-19 pneumonia. Both patients were in good clinical condition before the infection and were receiving immunosuppression with calcineurin inhibitors (CNI), mycophenolate mofetil, and corticosteroids. Whereas mycophenolate mofetil was withdrawn in both cases, CNI were suspended only in the second patient. The first patient always maintained excellent oxygen saturation throughout hospitalization with no need for additional oxygen therapy. He was discharged with a satisfactory pulmonary function and a complete resolution of radiological and clinical findings. However, at discharge SARS-CoV-2 RNA could still be detected in the nasopharyngeal swab and in the stools. The second patient required mechanical ventilation, had a progressive deterioration of his clinical conditions, and had a fatal outcome. Further insight into SARS-CoV-2 infection is eagerly awaited to improve the outcome of transplant recipients affected by COVID-19 pneumonia.

Acute infectious osteomyelitis in children: new treatment strategies for an old enemy.

BACKGROUND: Acute osteomyelitis still represents a significant clinical challenge, with an increasing incidence in paediatric population. A careful assessment and a rapid diagnosis with proper timing and choice of empirical antimicrobial therapy are necessary to avoid sequelae. The initial treatment should consist of empirical antibiotic therapy, to cover the major responsible pathogens in each age group. DATA SOURCES: We made a literature search with PubMed and Cochrane database from 2000 to 2019 in English, French, and Spanish languages using the key words "osteomyelitis, children, clinical, diagnosis, and treatment". RESULTS: The child's clinical features, age, and the microbiological profile of the geographic area should be evaluated for diagnosis and in the choice of antibiotic treatment. Latest data suggest the administration of intravenous antibiotics for a short period, with subsequent oral therapy, according to the improvement of clinical status and inflammatory markers. For children older than 3 months, the shift to oral medications is already possible after a short course of intravenous therapy, until recovery. The timing for the shift from cefazolin to cephalexin or cefuroxime, intravenous clindamycin to oral clindamycin, and intravenous ceftriaxone + oxacillin to oral equivalents will be decided according to the improvement of clinical status and inflammatory markers. We also present the approach to osteomyelitis due to difficult pathogens, such as Methicillin-resistant Staphylococcus aureus (MRSA) and Panton-Valentine leukocidin (PVL)-positive S. aureus infections. CONCLUSION: In this review, we present the current approach to the clinical diagnosis and management of osteomyelitis in childhood, with an update on recent recommendations, as a useful instrument to understand the rationale of antibiotic therapy.

Training in pediatric palliative care in Italy: still much to do.

AIM: This survey investigated the availability of training programs in pediatric palliative care (PPC) for Italian postgraduates specializing in pediatric medicine. METHODS: Two questionnaires were developed: (i) a questionnaire addressed to the Directors of Italian postgraduate pediatric medicine programs (n = 37); and (ii) a survey to the postgraduate students in pediatric medicine at the University Hospitals of Padua and Udine (n = 127). RESULTS: 14 directors participated (response rate: 37.8%). In 85.7% of cases (n = 12), lectures on PPC were offered, for a supposed maximum of 90 minutes/year. 116 students responded (response rate: 91%): they stated that, approximately 40 min/year of training on PPC was provided. In total, 37% of responders stated they attended a PPC Service during their training. The majority of responders (68.1%, n = 79) did not feel ready to care for a pediatric patient with life-limiting disease. CONCLUSIONS: Although PPC is well-recognized as part of a pediatrician's training, it receives poor attention.

Pain in Mucopolysaccharidoses: Analysis of the Problem and Possible Treatments.

Mucopolysaccharidosis (MPS) are a group of lysosomal storage disorders that are caused by the deficiency of enzymes involving in the catabolism of glycosaminoglycan (GAGs). GAGs incompletely degraded accumulate in many sites, damaging tissues and cells, leading to a variety of clinical manifestations. Many of these manifestations are painful, but few data are available in the literature concerning the prevalence, etiology, and pathogenesis of pain in children with MPS. This review, through the analysis of the data available the in literature, underscores the relevant prevalence of pain in MPSs' children, provides the instruments to discern the etiopathogenesis of the disease and of pain, illustrates the available molecules for the management of pain and the possible advantages of non-pharmacological pain therapy in MPSs' patients.

Needle-related pain and distress management during needle-related procedures in children with and without intellectual disability.

Children with intellectual disability frequently undergo needle-related procedures for diagnosis or treatment. Nevertheless, only a few studies deal with pain and distress management during the procedure in this population of children. This study aimed to investigate the number of anxiety and pain management techniques performed during needle procedure in children with intellectual disability (cases) compared to a population of children without intellectual disability (controls). This multicenter cohort study was performed from July 2016 to January 2018 in the pediatric ward of four urban hospitals in Italy. Eligible subjects were children with and without intellectual disability, from 4 to 17 years old, who needed venipuncture or intravenous cannulation for diagnosis or treatment. Use of topical anesthesia, distraction techniques, and physical or verbal comfort during procedures were recorded. Pain and anxiety scores were also recorded. Forty-seven cases and 94 controls were recruited. Three pain- and anxiety-relieving techniques were performed during the procedure in 12 (25%) cases and in 10 controls (11%); two techniques were performed in 23 (50%) cases and in 26 (28%) controls; 12 (25%) cases and 52 (55%) controls received only one.Conclusion: In this series, children with intellectual disability received significantly more relieving techniques, but experienced more pain and anxiety when compared to children without intellectual disability. What is Known: • Children with intellectual disability experience more episodes of pain than cognitively healthy ones, and almost 10% of these episodes are due to medical procedures. What is New: • Children with intellectual disability despite receiving more relieving techniques during a needle-related procedure experienced more pain and anxiety when compared to healthy children.

The PIPER WEEKEND study. Children's and adults satisfaction regarding paediatric pain in Italian Emergency Department.

BACKGROUND: Despite pain being a crucial aspect of urgent-emergency care, the attention of healthcare workers towards this symptom in the Emergency Department (ED) is still inadequate. The aims of this study were to assess children's and their adults accompanier's satisfaction regarding pain management in Italian ED, considering healthcare workers' attention to the symptom as well as the appropriateness and efficacy of treatments received. METHODS: Questionnaires were administered face-to-face by trained interviewers over the period of one weekend in 29 Italian ED. The questionnaires were addressed to children 3-16 years old, assigned a green code at triage, and their adult accompaniers. RESULTS: Overall, 1581 questionnaires were administered (923 to parents or caregivers, 658 to children). The reported level of attention to pain by the care team was high (57.20%) as was the adults' satisfaction with the pain management (95.01%); a high level of satisfaction was related to the healthcare workers' attention to pain. According to the adults, 73.56% of the healthcare professionals collected accurate information about pain; this was confirmed by the children. Pain was managed by a doctor-and-nurse team in less than half the cases (43.77%). Therapy efficacy was reportedly poor: only 14.01% of children were pain-free when leaving the ED. CONCLUSIONS: Despite increasing understanding of pain and the availability of guidelines and effective analgesics, efficient pain relief in paediatric patients in the ED remains an unfulfilled goal: half of children with pain did not receive any treatments. Therefore the quality of pain management in the ED needs to be improved.

Multicentre emergency department study found that paracetamol and ibuprofen were inappropriately used in 83% and 63% of paediatric cases.

AIM: The Pain Practice in Italian Paediatric Emergency Departments assessed how appropriately analgesic drugs were being used by Italian clinicians, based on national paediatric pain guidelines. METHODS: This was a retrospective study that involved 17 Italian members of the Pain In Pediatric Emergency Rooms group. It comprised patients up to the age of 14 years who came to hospital emergency departments with pain and were treated with paracetamol, ibuprofen or opioids, such as codeine, tramadol and morphine. RESULTS: We studied 1471 patients who were given 1593 doses of analgesics. The median time to administration of analgesia was 25 minutes. Opioids were used in 13.5% of the children, and usage increased with age and with more severe clinical conditions, such as trauma: 1.6% of children under two years, 5.9% aged 3-10 and 8.0% aged 11-14. Inappropriate doses of paracetamol, ibuprofen and opioids were used in 83%, 63% and 33% of cases, respectively. The patient's age was a critical determinant of the correct analgesic dosage; for every one-year increase in the patient's age, the probability of appropriate prescriptions rose 14.8%. CONCLUSION: The appropriate use of paracetamol and ibuprofen for paediatric pain in Italian emergency departments was very poor, but improved with age.

The Complexity of Pain Management in Children Affected by Mucopolysaccharidoses.

Mucopolysaccharidoses (MPSs) are a group of rare, genetic lysosomal storage disorders. They are caused by deficiencies of the lysosomal enzymes involved in the degradation of glycosaminoglycans (GAGs). Pain is a common feature in mucopolysaccharidoses. However, the pathophysiology of pain in this group of diseases is still unclear and genesis of pain is multifactorial. Currently, poor data about pain management in these patients are available. Here, we present our clinical experience in complex pain management in three children with MPS.

Barriers to the development of pediatric palliative care in Italy.

INTRODUCTION: In recent years the emergence of new types of patient, clinical situations, technological frontiers and "health" objectives have changed considerably the needs of ill children, this also concerns pediatric palliative care (PPC). In Italy, despite the introduction of legislation (Law 38/2010) stipulating the right of children and families to access appropriate services for pain control and pediatric palliative care, the availability of these services is still limited. AIM: The aim of this study is to highlight, through a review of the existing data and published literature, the critical issues that obstacle the planning and development of PPC services in Italy. RESULTS: Four main areas identified were: socio-cultural setting; types of patients and nature of diseases requiring PPC; training for PPC providers; regulatory and political issues. CONCLUSIONS: This type of analysis can provide the rational for advancing proposals and developing supportive, corrective and implementation strategies.

Use of Zoledronic Acid in Paediatric Craniofacial Fibrous Dysplasia.

We describe a case of a paediatric patient affected by mandibular fibrous dysplasia (FD) with severe and chronic pain who was successfully treated with zoledronic acid (ZOL): a third-generation bisphosphonate. Further research is needed to assess its safety and efficacy as a treatment option for FD in the paediatric population.

Use of Scrambler Therapy in Acute Paediatric Pain: A Case Report and Review of the Literature.

We report our clinical experience on the effect of Scrambler Therapy (ST) for a child with acute mixed pain refractory to pharmacological treatment. ST, recently proposed as an alternative treatment for chronic neuropathic pain in adults, is a noninvasive approach to relieve pain, by changing pain perception at brain level. It is safe and has no side effects. Further research is needed to assess its efficacy for acute pain and for paediatric population.