Noninvasive Ventilatory Support Research Articles

Impact of low dose inhaled nitric oxide treatment in spontaneously breathing and intubated COVID-19 patients: a retrospective propensity-matched study

BackgroundThe benefit of Inhaled nitric oxide (iNO) therapy in the setting of COVID-19-related ARDS is obscure. We performed a multicenter retrospective study to evaluate the impact of iNO on patients with COVID-19 who require respiratory support.MethodsThis retrospective multicenter study included COVID-19 patients enrolled in the SCCM VIRUS COVID-19 registry who were admitted to different Mayo Clinic sites between March 2020 and June 2022 and required high-flow nasal cannula (HFNC), non-invasive ventilation (NIV), or invasive mechanical ventilation (IMV). Patients were included in the ‘spontaneously breathing’ group if they remained non-intubated or were initiated on an HFNC (± NIV) before intubation. Patients who got intubated without prior use of an HFNC (± NIV) were included in the ‘intubated group.’ They were further divided into categories based on their iNO usage. Propensity score matching (PSM) and inverse propensity of treatment weighting (IPTW) were performed to examine outcomes.ResultsAmong 2767 patients included in our analysis, 1879 belonged to spontaneously breathing (153 received iNO), and 888 belonged to the intubated group (193 received iNO). There was a consistent improvement in FiO2 requirement, P/F ratio, and respiratory rate within 48 h of iNO use among both spontaneously breathing and intubated groups. However, there was no significant difference in intubation risk with iNO use among spontaneously breathing patients (PSM OR 1.08, CI 0.71–1.65; IPTW OR 1.10, CI 0.90–1.33). In a time-to-event analysis using Cox proportional hazard model, spontaneously breathing patients initiated on iNO had a lower hazard ratio of in-hospital mortality (PSM HR 0.49, CI 0.32–0.75, IPTW HR 0.40, 95% CI 0.26–0.62) but intubated patients did not (PSM HR: 0.90; CI 0.66–1.24, IPTW HR 0.98, 95% CI 0.73–1.31). iNO use was associated with longer in-hospital stays, ICU stays, ventilation duration, and a higher incidence of creatinine rise.ConclusionsThis retrospective propensity-score matched study showed that spontaneously breathing COVID-19 patients on HFNC/ NIV support had a decreased in-hospital mortality risk with iNO use in a time-to-event analysis. Both intubated and spontaneously breathing patients had improvement in oxygenation parameters with iNO therapy but were associated with longer in-hospital stays, ICU stays, ventilation duration, and higher incidence of creatinine rise.

Average volume-assured pressure support versus fixed pressure support in chronic hypercapnic respiratory failure: a systematic review and meta-analysis

Rationale: Chronic hypercapnic respiratory failure occurs due to alveolar hypoventilation resulting in carbon dioxide retention. This is commonly managed with noninvasive ventilation (NIV) with modalities including fixed pressure support and average volume-assured pressure support (AVAPS). However, there is limited information comparing outcomes with these two modes of ventilator support in the management of chronic hypercapnic respiratory failure. Objective: This review and meta-analysis analyze the outcomes with fixed pressure NIV versus average volume-assured pressure support NIV in managing chronic obstructive pulmonary disease (COPD) with chronic hypercapnic respiratory failure, focusing on patients’ perception of symptom burden and gas exchange based on arterial blood gases. Search methods: PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science databases were searched; the latest search date was December 1, 2023. Inclusion criteria: randomized control trials and crossover studies in English in adults over the age of 19 with the diagnosis of COPD and chronic hypercapnic respiratory failure. Exclusion criteria: patients less than 19 years old, patients with acute exacerbations, and patients with central respiratory failure or neuromuscular disease. Outcomes included blood gas analysis after use of NIV measured in mmHg and patient perception of mental health, symptom burden, and comfort. Results for each outcome were analyzed in RevMan using an inverse variance statistical method with a fixed effect analysis. The final analysis included 7 studies with 252 participants. Results: The patients were 64 ± 9 years old. Baseline pulmonary function testing showed a forced expiratory volume in the first second (FEV1) of 34.6 ± 14.2 % predicted, consistent with severe COPD per GOLD criteria, and a baseline PaCO2 of 55.2 ± 9.2 mmHg. Primary outcomes for ventilation showed no statistical difference between AVAPS and fixed pressure support groups in PaCO2 (Odds Ratio [OR] -1.51; 95% Confidence Interval [CI]: -3.18, 0.16; p=0.08). Patient perceived outcomes were evaluated using several questionnaires, including St. George Respiratory Questionnaire (SGRQ), Short Form 36 Health Survey Questionnaire (SF-36), and Visual Analogue Scale (VAS). Comparable results were not available for all studies, but no statistically significant differences were found when comparing study results. Conclusions: There was little or no clinically significant difference between fixed pressure support and AVAPS in gas exchange. There are inadequate data to draw conclusions about the effect of fixed pressure support compared to AVAPS on patient perceived outcomes, such as comfort and symptom burden. No studies evaluated mortality benefit, cost effectiveness, or hospitalizations. Key words: COPD, chronic hypercapnic respiratory failure, non-invasive ventilation, average volume-assured pressure support ventilation

Myocardial Ischemia after Severe Scorpion Envenomation: A Narrative Review.

Myocardial ischemia after severe scorpion envenomation is rarely reported. The aim of this review was to elaborate on a review of myocardial ischemia after severe scorpion envenomation and to detail the mechanism of this myocardial hypoperfusion. We used the PubMed database and entered the following keywords in MeSH research: scorpion envenomation, myocardial ischemia, myocardial perfusion scintigraphy, echocardiography, and troponins. The literature analysis confirmed that severe scorpion envenomation can be complicated by temporary myocardial ischemia, based on electrocardiographic, histopathologic, echocardiographic, myocardial perfusion scintigraphy, and biological studies. The correlation between clinical manifestations, laboratory and electrocardiographic evidence of myocardial damage, echocardiographic studies, perfusion scintigraphy abnormalities, and histopathologic findings are suggestive of lesions of cardiac fibers secondary to myocardial ischemia. Myocardial hypoperfusion may be due to multiple factors. First, catecholamine storms can induce microvascular constriction. On the other hand, the release of catecholamines through a complex neurohormonal interaction with other neuropeptides and cytokine release can produce/induce major coronary microvascular constriction and/or microvascular injury, leading to microvascular acute coronary syndrome with Takotsubo cardiomyopathy. The management of severe scorpion envenomation with severe myocardial failure and pulmonary edema is based on oxygen with invasive or noninvasive ventilator support. Dobutamine improves cardiac function after scorpion envenomation. Antiplatelet therapy is not recommended. In conclusion, severe scorpion envenomation can be complicated by temporary myocardial ischemia, which can be due to multiple factors.

Short Survival of Patients with Chronic Obstructive Pulmonary Disease and a Do-Not-Resuscitate Order Despite the Noninvasive Positive Pressure Ventilatory Support: A Retrospective Cohort Study in Taiwan

Short Survival of Patients with Chronic Obstructive Pulmonary Disease and a Do-Not-Resuscitate Order Despite the Noninvasive Positive Pressure Ventilatory Support: A Retrospective Cohort Study in Taiwan

Protective mechanical ventilation in critically ill patients after surgery

Purpose of review This review aims to provide an updated overview of lung protective strategies in critically ill patients after surgery, focusing on the utility of postoperative open-lung ventilation during the transition from the operating room to the intensive care unit. Recent findings Mechanically ventilated patients after surgery represent a challenge in the intensive care unit. Different protective strategies have been proposed to minimize the risk of ventilator-induced lung injury (VILI) and facilitate adequate weaning from mechanical ventilation. Fast-track extubation protocols, increasingly standard in the care of critically ill patients postsurgery, have demonstrated improvements in recovery and reductions in acute lung injury, primarily based on retrospective studies. Open-lung ventilation strategies, such as individualization of positive-end expiratory pressure based on driving pressure and postoperative noninvasive ventilation support with high-flow nasal cannula, are becoming standard of care in high-risk surgical patients after major abdominal or thoracic surgeries. Summary Mechanical ventilation in surgical patients should adhere to lung protective strategies (i.e., individualizing positive end expiratory pressure and prioritize alveolar recruitment) during the transition from the operating room to the intensive care unit.

Assessment of right ventricular sequelae by speckle tracking echocardiography in recovered COVID-19 patients

Background TTE is the main modality used to assess RV function, but conventional TTE parameters have limited diagnostic value because they may fail to detect early abnormalities in RV systolic function. Due to its ability to detect subclinical impairment of cardiac function, 2D STE has been widely used to investigate RV function. In this study, we aimed to investigate whether there are sequelae of RV function in recovered COVID-19 patients with pulmonary involvement. Methods This is a prospective observational cohort study of 57 healthy volunteers and 54 patients. Participants had no history of chronic illness and no evidence of respiratory or cardiac symptoms. The patients had been hospitalised with COVID-19 with pulmonary involvement but did not require intensive care unit follow-up or non-invasive mechanical ventilation support. TTE was performed. Demographic and clinical characteristics and laboratory test results were collected. Results LVEF, TAPSE, St and FAC were significantly lower in the patient group. LV-LS 3-chamber, LV-GLS, RV-FWS, RV-GLS were significantly lower in the patient group. Conclusions RV-LS and LV-GLS were shown to decrease in the patient group. Although no obvious pathological values were observed in RV parameters on conventional echocardiography, TAPSE, St and FAC values were lower in the patient group.

Accuracy and Interpretation of Transcutaneous Carbon Dioxide Monitoring in Critically Ill Children.

Transcutaneous carbon dioxide (Tc co2 ) monitoring can noninvasively assess ventilation by estimating carbon dioxide ( CO2 ) levels in the blood. We aimed to evaluate the accuracy of Tc co2 monitoring in critically ill children by comparing it to the partial pressure of arterial carbon dioxide (Pa co2 ). In addition, we sought to determine the variation between Tc co2 and Pa co2 acceptable to clinicians to modify patient care and to determine which patient-level factors may affect the accuracy of Tc co2 measurements. Retrospective observational cohort study. Single, quaternary care PICU from July 1, 2012, to August 1, 2020. Included participants were admitted to the PICU and received noninvasive ventilation support (i.e., continuous or bilevel positive airway pressure), conventional mechanical ventilation, or high-frequency oscillatory or percussive ventilation with Tc co2 measurements obtained within 15 minutes of Pa co2 measurement. None. Three thousand four hundred seven paired arterial blood gas and Tc co2 measurements were obtained from 264 patients. Bland-Altman analysis revealed a bias of -4.4 mm Hg (95% CI, -27 to 18.3 mm Hg) for Tc co2 levels against Pa co2 levels on the first measurement pair for each patient, which fell within the acceptable range of ±5 mm Hg stated by surveyed clinicians, albeit with wide limits of agreement. The sensitivity and specificity of Tc co2 to diagnose hypercarbia were 93% and 71%, respectively. Vasoactive-Infusion Score (VIS), age, and self-identified Black/African American race confounded the relationship between Tc co2 with Pa co2 but percent fluid overload, weight-for-age, probe location, and severity of illness were not significantly associated with Tc co2 accuracy. Tc co2 monitoring may be a useful adjunct to monitor ventilation in children with respiratory failure, but providers must be aware of the limitations to its accuracy.

The Effect of Two Different Nasal Interfaces Used in Post-Extubation Non-Invasive Respiratory Support on Extubation Success in Newborns

Background: Non-invasive ventilation support is frequently used in newborns after extubation. The efficiency of non-invasive ventilation support is associated to type of nasal interface used. We aimed to investigate the effect of nasal interface type in our study on extubation success. Materials and Methods: We retrospectively evaluated a total of 105 term and preterm patients who were extubated to non-invasive ventilation. We divided the patients into two groups according to nasal interface type: RAM cannula or short binasal prongs (SBPs). We examined extubation failure between the two groups. Results: While 63 of the patients were in RAM cannula group, 42 of them were in SBPs group, and the demographic characteristics of the patients were similar. There was no statistically significant differen-ce in the extubation failure rates between the groups (RAM; %44.4 vs SBPs; %38.1, p=0.518). The Ram cannula group had a higher beginning median positive end-expiratory pressure value (7.0 vs 6.5 cmH2O, p=0.038; respectively) and a lower median respiratory rate (60 vs 62/minute, p=0.032; res-pectively) than the SBPs group. Conclusions: We believe that the easy-to-use RAM cannula can be used in selected patients, especially by setting the PEEP value approximately 1 cmH2O higher.

May Recovered COVID-19 Patients Have Impaired Myocardial Work?

Background: The aim of this study was to investigate whether there are sequelae in left ventricular (LV) systolic function by comparing LV function in fully recovered COVID-19 patients with pulmonary involvement and healthy controls without COVID-19 by conventional echocardiography and myocardial work. Materials and Methods: 55 healthy volunteers and 61 patients hospitalized with COVID-19 with pulmonary in-volvement were included. Patients did not need non-invasive or invasive mechanical ventilation support during hospitalization. Patients were included in the study if they were asymptomatic for at least six months after recov-ery from COVID-19. Transthoracic echocardiography (TTE) was performed. Demographic and clinical characteris-tics and laboratory test results were collected. Clinical characteristics, blood tests, TTE, speckle-tracking echocar-diography (STE) and myocardial work results were compared. Results: No statistically significant differences were found in the longitudinal strain parameters of the LV among the study groups. The patient group exhibited notably reduced levels of global work index (GWI), global con-structed work (GCW), and global work efficiency (GWE). The patient group exhibited a notably elevated global wasted work (GWW). Conclusions: The group of fully recovered asymptomatic COVID-19 patients with pulmonary involvement showed significantly lower values for GWI, GCW, and GWE, while GWW showed a significantly higher value. Myocardial work parameters may be useful in determining myocardial sequelae.

Evaluation and Prevention of Perioperative Respiratory Failure.

Respiratory failure is a common perioperative complication. The risk of respiratory failure can be reduced with effective preoperative evaluation, preventative measures, and knowledge of evidence-based management techniques. Effective preoperative screening methods include ARISCAT scoring, OSA screening, and the LAS VEGAS score (including the ASA physical status score). Evaluation by the six-minute walk test and a routine pulmonary physical exam has been shown to be effective at predicting postoperative pulmonary complications, whereas evidence on the predictive power of pulmonary function tests and chest radiography has been inconclusive. Preoperative smoking cessation and lung expansion maneuvers have been shown to decrease the risk of pulmonary complications postoperatively. Intraoperative management techniques that decrease the pulmonary complication risk include neuromuscular blockade reversal with sugammadex, limiting surgical times to less than 3 h when possible, lung-protective ventilation techniques, and multimodal analgesia to decrease opioid usage. In the immediate postoperative period, providers should be prepared to quickly treat bronchospasm, hypoventilation, and upper airway obstruction. For post-surgical patients who remain in the hospital, the risk of pulmonary complications can be decreased with lung expansion techniques, adequate analgesia, automated continuous postoperative ward monitoring, non-invasive ventilatory support, and early mobilization. This article was written to analyze the available literature on this topic in order to learn and practice the prevention of perioperative respiratory failure when caring for patients on a daily basis.

How to ventilate critically ill children with cancer?: a narrative review

Abstract The management of respiratory failure and hypoxemia in children with cancer presents a critical challenge. Choosing between invasive and noninvasive mechanical ventilation can profoundly impact mortality rates, especially in resource-limited settings. Choosing between invasive and noninvasive mechanical ventilation can impact mortality rates, particularly in resource-limited settings. Extensive clinical studies are imperative to thoroughly evaluate the efficacy of invasive mechanical ventilation (IMV) and noninvasive ventilation (NIV) during the early stages of treatment. Further research is crucial to determine the most optimal therapeutic approach. Early implementation of IMV or NIV could significantly reduce mortality rates in these patients.[ 1 ] Additionally, this article examines the admission of children with terminal cancer, evaluating their use of invasive and noninvasive ventilatory support versus palliative care. The interdisciplinary medical team, in collaboration with the family, must carefully consider the benefits and risks of these interventions, whether in the early or terminal stages of the disease. Furthermore, the article delves into the controversies surrounding the utilization of ventilation in critically ill children with cancer.

Utility of HACOR Score in Patients with Acute Exacerbation of Post-tuberculosis Obstructive Airway Disease: A Retrospective Observational Study.

In this study, we tried to analyze the utility of the HACOR score in the acute exacerbation of post-tuberculosis obstructive airway disease (post-TB-OAD). The HACOR score for patients in acute exacerbation of post-TB-OAD who needed noninvasive ventilation (NIV) support was calculated at 1, 12, 24, and 48 hours. The history of NIV success or failure was noted. Using a cutoff score of >5, the sensitivity, specificity, positive predictive value, and negative predictive value were calculated. The receiver operating characteristic (ROC) curve was plotted based on the HACOR score 1 hour after the NIV trial. In subjects requiring NIV for up to 2 days, the trend in the HACOR score was analyzed using a paired t-test. A total of 38 out of 100 patients belonged to the NIV failure group. The mean HACOR score at 1 hour was 9.47 in the NIV failure group. The sensitivity was 89.47%, and the specificity was 87.09% for a score of >5. The positive predictive value and negative predictive value were 80.95 and 93.10%, respectively. The area under the curve (AUC) for the ROC was 0.853. The mean score showed an upward trend in the NIV failure group and a downward trend in the NIV success group. The change in the score in the NIV success group was statistically significant (t = -4.290, p-value = 0.00044). The HACOR score can predict NIV failure in patients with acute exacerbation of post-TB-OAD.

Pregnancy and COVID—Complications and its Challenges: A Case Series from a Tertiary Care Center in the Northeastern Part of India

The objective was to describe the course of management of all the coronavirus disease 2019 (COVID-19)-positive pregnant women, admitted to a 150-bedded tertiary care center in Guwahati, Assam, from March 01, 2021, till June 15, 2021. We collected a case series of 13 COVID-19-positive pregnant women, mostly in their second and third trimesters, admitted to our center between March 01, 2021, and June 15, 2021. All of the cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were confirmed by a positive result on real-time reverse transcriptase-polymerase chain reaction (RT-PCR) tests. We aimed to show the course of management and maternal outcomes in these cases. The Results show that among the 13 infected pregnant women, three presented with severe SARS-CoV-2 pneumonia and were treated in the intensive care unit (ICU) and the rest were treated in wards as the mild category and discharged successfully. Two among them required invasive mechanical ventilation (IMV), and one was managed on non-invasive ventilation (NIV). Of the two mechanically ventilated patients, one succumbed to the illness and the other patient was successfully weaned in 5 days and shifted out after 15 days of the ICU stay. The third patient was on NIV support for 7 days, weaned off to low-flow oxygen therapy via face mask/ nasal prongs, and shifted out after 17 days of the ICU stay. Data on pregnant women with coronavirus infection are scarce and contradictory as the effect of SARS-CoV-2 on pregnancy is not clear. It is highly important to systemically investigate the clinical characteristics and outcomes of pregnant women with COVID-19 to provide strong guidelines for prevention, treatment, and management.

Persistent Residual Lung Abnormalities (PRLAs) as Post COVID Lung Sequel in Recovered Severe Pneumonia Case with Lung Function Abnormality at Two Year Follow Up

Coronavirus related (SARS-CoV-2) global pandemic has caused significant mortality and morbidity globally in the last three years. Although, pandemic has waned since last year, we are not in great peace of relief due to lingering effects of COVID-19 persisted even after two years of illness. Radiological phenotypes are radiological patterns or observable characteristics of COVID-19 pneumonia. Radiological outcomes are initially interpreted as post covid lung fibrosis in short term follow-up of recovered COVID-19 cases in post covid care settings and during long term evaluation these abnormalities are defined as post covid sequalae’s. In present case report, 38-year male, presented in outdoor unit for shortness of breath on exertion with history of severe COVID-19 Pneumonia resulted into acute respiratory distress syndrome with hospitalization in intensive care unit one year back and required high flow nasal cannula (HFNC) with Non-invasive ventilatory support (NIV) for two weeks. He was offered oxygen supplementation at home with antibiotics for three months and no requirement of oxygen and some respiratory symptoms even after one year. His HRCT thorax documented at one year of discharge from hospital revealed typical interstitial opacities labelled as Persistent Residual lung abnormalities (RLAs) which are predominantly reticular and linear opacities in peripheral parts of lungs without honeycombing within typical pleural based areas with parenchymal bands and minimally altered lung architecture and preserved lung volume.

Outcomes and Impact of Pre-ECMO Clinical Course in Severe COVID-19-Related ARDS Treated with VV-ECMO: Data from an Italian Referral ECMO Center.

Background: The efficacy of veno-venous extracorporeal membrane oxygenation (VV-ECMO) as rescue therapy for refractory COVID-19-related ARDS (C-ARDS) is still debated. We describe the cohort of C-ARDS patients treated with VV-ECMO at our ECMO center, focusing on factors that may affect in-hospital mortality and describing the time course of lung mechanics to assess prognosis. Methods: We performed a prospective observational study in the intensive care unit at the "Città della Salute e della Scienza" University Hospital in Turin, Italy, between March 2020 and December 2021. Indications and management of ECMO followed the Extracorporeal Life Support Organization (ELSO) guidelines. Results: The 60-day in-hospital mortality was particularly high (85.4%). Non-survivor patients were more frequently treated with non-invasive ventilatory support and steroids before ECMO (95.1% vs. 57.1%, p = 0.018 and 73.2% vs. 28.6%, p = 0.033, respectively), while hypertension was the only pre-ECMO factor independently associated with in-hospital mortality (HR: 2.06, 95%CI: 1.06-4.00). High rates of bleeding (85.4%) and superinfections (91.7%) were recorded during ECMO, likely affecting the overall length of ECMO (18 days, IQR: 10-24) and the hospital stay (32 days, IQR: 24-47). Static lung compliance was lower in non-survivors (p = 0.031) and differed over time (p = 0.049), decreasing by 48% compared to initial values in non-survivors. Conclusions: Our data suggest the importance of considering NIS among the common ECMO eligibility criteria and changes in lung compliance during ECMO as a prognostic marker.

In Vivo Measurement of Tidal Volume During Non-invasive Respiratory Support by Continuous-Flow Helmet CPAP

Recently, the interest in the Helmet interface during non-invasive respiratory support (NIRS) has increased due to the COVID-19 pandemic. During NIRS, positive end-expiratory pressure (PEEP) can be given as continuous positive airway pressure (CPAP), which maintains a positive airway pressure throughout the whole respiratory cycle with Helmet as an interface (H-CPAP). The main disadvantage of the H-CPAP is the inability to measure tidal volume (VT). Opto-electronic plethysmography (OEP) is a non-invasive technique that is not sensitive to gas compression/expansion inside the helmet. OEP acquisitions were performed on 28 healthy volunteers (14 females and 14 males) at baseline and during Helmet CPAP. The effect of posture (semi-recumbent vs. prone), flow (50 vs. 60 L/min), and PEEP (0 vs. 5 vs. 10 cmH2O) on the ventilatory and thoracic-abdominal pattern and the operational volumes were investigated. Prone position limited vital capacity, abdominal expansion and chest wall recruitment. A constant flow of 60 L/min reduced the need for the subject to ventilate while having a slight recruitment effect (100 mL) in the semi-recumbent position. A progressive increasing recruitment was found with higher PEEP but limited by the prone position. It is possible to accurately measure tidal volume during H-CPAP to deliver non-invasive ventilatory support using opto-electronic plethysmography during different clinical settings.

Congenital Central Hypoventilation Syndrome: neonatal diagnosis and management

To report a neonatal case successfully treated with non-invasive ventilatory support (NVS), avoiding tracheostomy. Full-term newborn, whose mother uses nocturnal NVS due to CCHS. During the transition period, she presented desaturations associated with hypercapnia and respiratory acidosis, without pulmonary involvement. She developed severe hypoventilation during sleep, with no respiratory effort, peripheral oxygen saturation (SpO2) < 80%, plus respiratory acidosis. While awake, she had good respiratory effort and normal SpO2 without assistance. Noninvasive continuous positive airway pressure and oxygen therapy worsened her condition while sleeping. Complete NVS with nasal interface and bi-level airway positive pressure, inspiratory/expiratory pressure 14-16/4 cm H2O, normalized SpO2 during sleep, and arterial blood gases while awake. Sequencing of the PHOX2B gene confirmed the presence of a heterozygous pathogenic variant with the 20/26 genotype. At 2 months of age, she was discharged maintaining NVS with nasal interface and 0 PEEP, achieving adequate neurodevelopment. We highlight the importance of genetic diagnosis of CCHS in neonates with clinical presentation of early alveolar hypoventilation, especially if there is a family history. We are not aware of other reports of neonatal onset in which NVS prevents IMV, in this potentially lethal pathology.

Comparison of clinical features of cystic fibrosis patients eligible but not on CFTR modulators to ineligible for CFTR modulators.

Cystic fibrosis transmembrane conductance regulator (CFTR) modulator drugs target the underlying defect and improve CFTR function. They are a part of standard care in many countries, but not all patients are eligible for these drugs due to age and genotype. Here, we aimed to determine the characteristics of non-eligible patients for CFTR modulators in the CF registry of Turkey (CFRT) to highlight their clinical needs. This retrospective cohort study included CF patient data from the CFRT in 2021. The decision of eligibility for the CFTR modulator was determined according to the 'Vertex treatment-Finder' on the Vertex® website. Demographic and clinical characteristics of patients were compared between eligible (group 1) and ineligible (group 2) groups for CFTR modulators. Among the study population (N = 1527), 873 (57.2%) were in group 1 and 654 (42.8%) were in group 2. There was no statistical difference between groups regarding sex, meconium ileus history, diagnoses via newborn screening, FEV1 z-score, CF-associated complications, organ transplant history, and death. Patients in group 2 had a higher incidence of pancreatic insufficiency (87.7% vs. 83.2%, p = .010), lower median height z-scores (-0.87 vs. -0.55, p < .001), lower median body mass index z-scores (-0.65 vs. -0.50, p < .001), longer days receiving antibiotics due to pulmonary exacerbation (0 [interquartile range, IQR: 0-2] vs. 0 [IQR: 0-7], p = 0.001), and more non-invasive ventilation support (2.6% vs. 0.9%, p = 0.008) than patients in group 1. The ineligible group had worse clinical outcomes than the eligible group. This highlights their need for life-changing drugs to improve clinical outcomes.

A Phase I trial of Non-invasiveVentilationand seizure prophylaxis with levetiracetam InChildren withCerebral Malaria Trial (NOVICE-M Trial).

African children with cerebral malaria and seizures caused Plasmodium falciparum are at greater risk of poor outcomes including death and neurological sequelae. The agonal events are severe hypoventilation and respiratory arrest often triggered by seizures. We hypothesised that prophylactic anti-seizure medication (ASM) could avert 'spikes' of intracranial pressure during or following seizures and that adequate ventilation could be supported by biphasic Cuirass Ventilation (BCV) which requires no intubation. A Phase I trial conducted in Kilifi, Kenya designed to provide data on safety, feasibility and preliminary data on seizure control using prophylactic ASM (levetiracetam) and BCV as non-invasive ventilatory support in children with cerebral malaria. Children aged 3 months to 12-years hospitalised with P falciparum malaria (positive rapid diagnostic test or a malaria slide), a Blantyre Coma Score ≤2 and a history of acute seizures in this illness are eligible for the trial. In a phased evaluation we will study i) BCV alone for respiratory support (n=10); ii) prophylactic LVT: 40mg/kg loading dose then 30mg/kg every 12 hours given via nasogastric tube for 72 hours (or until fully conscious) plus BCV support (n=10) and; iii) prophylactic LVT: 60mg/kg loading dose then 45mg/kg every 12 hours given via nasogastric tube for 72 hours (or until fully conscious) plus BCV support (n=10). Primary outcome measure: cumulative time with a clinically detected seizures or number of observed seizures over 36 hours. Secondary outcomes will be assessed by feasibility or ability to implement BCV, and recovery from coma within 36 hours. Safety endpoints include: aspiration during admission; death at 28 days and 180 days; and de-novo neurological impairments at 180 days. This is a Phase I trial largely designed to test the feasibility, tolerability and safety of using non-invasive ventilatory support and LVT prophylaxis in cerebral malaria. ISRCTN76942974 (5.02.2019); PACTR202112749708968 (20.12.2021).

Respiratory Support Practices for Bronchiolitis in the Pediatric Intensive Care Unit

Admissions to the pediatric intensive care unit (PICU) due to bronchiolitis are increasing. Whether this increase is associated with changes in noninvasive respiratory support practices is unknown. To assess whether the number of PICU admissions for bronchiolitis between 2013 and 2022 was associated with changes in the use of high-flow nasal cannula (HFNC), noninvasive ventilation (NIV), and invasive mechanical ventilation (IMV) and to identify factors associated with HFNC and NIV success and failure. This cross-sectional study examined encounter data from the Virtual Pediatric Systems database on annual PICU admissions for bronchiolitis and ventilation practices among patients aged younger than 2 years admitted to 27 PICUs between January 1, 2013, and December 31, 2022. Use of HFNC and NIV was defined as successful if patients were weaned to less invasive support (room air or low-flow nasal cannula for HFNC; room air, low-flow nasal cannula, or HFNC for NIV). The main outcome was the number of PICU admissions for bronchiolitis requiring the use of HFNC, NIV, or IMV. Linear regression was used to analyze the association between admission year and absolute numbers of encounters stratified by the maximum level of respiratory support required. Multivariable logistic regression was used to analyze factors associated with HFNC and NIV success and failure (defined as not meeting the criteria for success). Included in the analysis were 33 816 encounters for patients with bronchiolitis (20 186 males [59.7%]; 1910 patients [5.6%] aged ≤28 days and 31 906 patients [94.4%] aged 29 days to <2 years) treated at 27 PICUs from 2013 to 2022. A total of 7615 of 15 518 patients (49.1%) had respiratory syncytial virus infection and 1522 of 33 816 (4.5%) had preexisting cardiac disease. Admissions to the PICU increased by 350 (95% CI, 170-531) encounters annually. When data were grouped by the maximum level of respiratory support required, HFNC use increased by 242 (95% CI, 139-345) encounters per year and NIV use increased by 126 (95% CI, 64-189) encounters per year. The use of IMV did not significantly change (10 [95% CI, -11 to 31] encounters per year). In all, 22 381 patients (81.8%) were successfully weaned from HFNC to low-flow oxygen therapy or room air, 431 (1.6%) were restarted on HFNC, 3057 (11.2%) were escalated to NIV, and 1476 (5.4%) were escalated to IMV or extracorporeal membrane oxygenation (ECMO). Successful use of HFNC increased from 820 of 1027 encounters (79.8%) in 2013 to 3693 of 4399 encounters (84.0%) in 2022 (P = .002). In all, 8476 patients (81.5%) were successfully weaned from NIV, 787 (7.6%) were restarted on NIV, and 1135 (10.9%) were escalated to IMV or ECMO. Success with NIV increased from 224 of 306 encounters (73.2%) in 2013 to 1335 of 1589 encounters (84.0%) in 2022 (P < .001). In multivariable logistic regression, lower weight, higher Pediatric Risk of Mortality III score, cardiac disease, and PICU admission from outside the emergency department were associated with greater odds of HFNC and NIV failure. Findings of this cross-sectional study of patients aged younger than 2 years admitted for bronchiolitis suggest there was a 3-fold increase in PICU admissions between 2013 and 2022 associated with a 4.8-fold increase in HFNC use and a 5.8-fold increase in NIV use. Further research is needed to standardize approaches to HFNC and NIV support in bronchiolitis to reduce resource strain.