In utero ventilation induces lung parenchymal and vascular alterations in extremely preterm fetal sheep.

Extremely preterm infants are often exposed to long durations of mechanical ventilation to facilitate gas exchange, resulting in ventilation-induced lung injury (VILI). New lung protective strategies utilizing noninvasive ventilation or low tidal volumes are now common but have not reduced rates of bronchopulmonary dysplasia. We aimed to determine the effect of 24 h of low tidal volume ventilation on the immature lung by ventilating preterm fetal sheep in utero. Preterm fetal sheep at 110 ± 1(SD) days' gestation underwent sterile surgery for instrumentation with a tracheal loop to enable in utero mechanical ventilation (IUV). At 112 ± 1 days' gestation, fetuses received either in utero mechanical ventilation (IUV, n = 10) targeting 3-5 mL/kg for 24 h, or no ventilation (CONT, n = 9). At necropsy, fetal lungs were collected to assess molecular and histological markers of lung inflammation and injury. IUV significantly increased lung mRNA expression of interleukin (IL)-1ß, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF) compared with CONT, and increased surfactant protein (SP)-A1, SP-B, and SP-C mRNA expression compared with CONT. IUV produced modest structural changes to the airways, including reduced parenchymal collagen and myofibroblast density. IUV increased pulmonary arteriole thickness compared with CONT but did not alter overall elastin or collagen content within the vasculature. In utero ventilation of an extremely preterm lung, even at low tidal volumes, induces lung inflammation and injury to the airways and vasculature. In utero ventilation may be an important model to isolate the confounding mechanisms of VILI to develop effective therapies for preterm infants requiring prolonged respiratory support.NEW & NOTEWORTHY Preterm infants often require prolonged respiratory support, but the relative contribution of ventilation to the development of lung injury is difficult to isolate. In utero mechanical ventilation allows for mechanistic investigations into ventilation-induced lung injury without confounding factors associated with sustaining extremely preterm lambs ex utero. Twenty-four hours of in utero ventilation, even at low tidal volumes, increased lung inflammation and surfactant protein expression and produced structural changes to the lung parenchyma and vasculature.

Proportion of confluent B-Lines predicts respiratory support in term infants shortly after birth.

OBJECTIVE: To develop and evaluate the predictive value of a simplified lung ultrasound (LUS) method for forecasting respiratory support in term infants. METHODS: This observational, prospective, diagnostic accuracy study was conducted in a tertiary academic hospital between June and December 2023. A total of 361 neonates underwent LUS examination within 1 h of birth. The proportion of each LUS sign was utilized to predict their respiratory outcomes and compared with the LUS score model. After identifying the best predictive LUS sign, simplified models were created based on different scan regions. The optimal simplified model was selected by comparing its accuracy with both the full model and the LUS score model. RESULTS: After three days of follow-up, 91 infants required respiratory support, while 270 remained healthy. The proportion of confluent B-lines demonstrated high predictive accuracy for respiratory support, with an area under the curve (AUC) of 89.1% (95% confidence interval [CI]: 84.5-93.7%). The optimal simplified model involved scanning the R/L 1-4 region, yielding an AUC of 87.5% (95% CI: 82.6-92.3%). Both the full model and the optimal simplified model exhibited higher predictive accuracy compared to the LUS score model. The optimal cut-off value for the simplified model was determined to be 15.9%, with a sensitivity of 76.9% and specificity of 91.9%. CONCLUSIONS: The proportion of confluent B-lines in LUS can effectively predict the need for respiratory support in term infants shortly after birth and offers greater reliability than the LUS score model.

Maternal vaccination against COVID-19 and neonatal outcomes during Omicron: INTERCOVID-2022 study.

BACKGROUND: In early 2023, when Omicron was the variant of concern, we showed that vaccinating pregnant women decreased the risk for severe COVID-19-related complications and maternal morbidity and mortality. OBJECTIVE: This study aimed to analyze the impact of COVID-19 during pregnancy on newborns and the effects of maternal COVID-19 vaccination on neonatal outcomes when Omicron was the variant of concern. STUDY DESIGN: INTERCOVID-2022 was a large, prospective, observational study, conducted in 40 hospitals across 18 countries, from November 27, 2021 (the day after the World Health Organization declared Omicron the variant of concern) to June 30, 2022, to assess the effect of COVID-19 in pregnancy on maternal and neonatal outcomes and to assess vaccine effectiveness. Women diagnosed with laboratory-confirmed COVID-19 during pregnancy were compared with 2 nondiagnosed, unmatched women recruited concomitantly and consecutively during pregnancy or at delivery. Mother-newborn dyads were followed until hospital discharge. The primary outcomes were a neonatal positive test for COVID-19, severe neonatal morbidity index, severe perinatal morbidity and mortality index, preterm birth, neonatal death, referral to neonatal intensive care unit, and diseases during the neonatal period. Vaccine effectiveness was estimated with adjustment for maternal risk profile. RESULTS: We enrolled 4707 neonates born to 1577 (33.5%) mothers diagnosed with COVID-19 and 3130 (66.5%) nondiagnosed mothers. Among the diagnosed mothers, 642 (40.7%) were not vaccinated, 147 (9.3%) were partially vaccinated, 551 (34.9%) were completely vaccinated, and 237 (15.0%) also had a booster vaccine. Neonates of booster-vaccinated mothers had less than half (relative risk, 0.46; 95% confidence interval, 0.23-0.91) the risk of being diagnosed with COVID-19 when compared with those of unvaccinated mothers; they also had the lowest rates of preterm birth, medically indicated preterm birth, respiratory distress syndrome, and number of days in the neonatal intensive care unit. Newborns of unvaccinated mothers had double the risk for neonatal death (relative risk, 2.06; 95% confidence interval, 1.06-4.00) when compared with those of nondiagnosed mothers. Vaccination was not associated with any congenital malformations. Although all vaccines provided protection against neonatal test positivity, newborns of booster-vaccinated mothers had the highest vaccine effectiveness (64%; 95% confidence interval, 10%-86%). Vaccine effectiveness was not as high for messenger RNA vaccines only. Vaccine effectiveness against moderate or severe neonatal outcomes was much lower, namely 13% in the booster-vaccinated group (all vaccines) and 25% and 28% in the completely and booster-vaccinated groups, respectively (messenger RNA vaccines only). Vaccines were fairly effective in protecting neonates when given to pregnant women ≤100 days (14 weeks) before birth; thereafter, the risk increased and was much higher after 200 days (29 weeks). Finally, none of the neonatal practices studied, including skin-to-skin contact and direct breastfeeding, increased the risk for infecting newborns. CONCLUSION: When Omicron was the variant of concern, newborns of unvaccinated mothers had an increased risk for neonatal death. Neonates of vaccinated mothers had a decreased risk for preterm birth and adverse neonatal outcomes. Because the protective effect of COVID-19 vaccination decreases with time, to ensure that newborns are maximally protected against COVID-19, mothers should receive a vaccine or booster dose no more than 14 weeks before the expected date of delivery.

Helmet c-PAP Versus NIPPV in Association with Early Respiratory Physiotherapy and Mobilization for Treating SARS-CoV-2 ARDS: A Case-control Prospective Single-center Study.

Introduction: Early noninvasive respiratory support (NIRS) is correlated with a success rate of 60-75% in patients experiencing SARS-CoV-2 ARDS. We conducted a prospective case-control study to assess differences in outcomes between Helmet c-PAP (H-c-PAP) and noninvasive positive pressure ventilation (NIPPV). Methods: All patients with SARS-CoV-2 ARDS, treated with H-c-PAP or NIPPV between October 2021 and April 2022 were sampled. We recorded: demographics, comorbidities, clinical, respiratory, sepsis, NIRS parameters, and outcomes. A "NIRS team" followed the patients in respiratory support supplying them with early and timely intensive physiotherapy i-PKT as well. The Cox's proportional hazard model was applied for multivariate analyses. Results: 368 patients were admitted to our hospital medical ward. 85 patients were treated with H-c-PAP and 145 underwent NIPPV. 138 patients needing oxygen supplementation alone were excluded. The two groups were homogeneously distributed and ICU admission rates were lower in the H-c-PAP one (9.4 vs 11% P = .001) while mortality was higher in the NIPPV group (22.7 vs 9.4%, P = .001). The two multivariate models, that had overall mortality as primary outcome, identified age, H-c-PAP daily, i-PKT and ICU admission as independent variables impacting on the outcome. Age was no longer a significant independent predictor after the inclusion of elderly patients (age >80). The third model showed daily i-PKT could prevent ICU admission whereas the length of NIRS was inversely proportional to outcome. Conclusions: A "NIRS multidisciplinary team" made it possible to adopt an early and timely combination of NIRS and i-PKT resulting in the saving of both patient lives and ICU resources.

Use of high-flow nasal cannula versus other noninvasive ventilation techniques or conventional oxygen therapy for respiratory support following pediatric cardiac surgery: A systematic review and meta-analysis.

INTRODUCTION: Noninvasive respiratory support may be provided to decrease the risk of postextubation failure following surgery. Despite these efforts, approximately 3%-27% of infants and children still experience respiratory failure after tracheal extubation following cardiac surgery. This systematic review evaluates studies comparing the efficacy of high-flow nasal cannula to conventional oxygen therapy such as nasal cannula and other noninvasive ventilation techniques in preventing postextubation failure in this patient population. METHODS: A systematic and comprehensive search was conducted in major databases including MEDLINE, EMBASE, Web of Science, and Central. The search encompassed articles focusing on the prophylactic use of high-flow nasal cannula following tracheal extubation in pediatric patients undergoing cardiac surgery for congenital heart disease. The inclusion criteria for this review consisted of randomized clinical trials as well as observational, cohort, and case-control studies. RESULTS: A total of 1295 studies were screened and 12 studies met the inclusion criteria. These 12 studies included a total of 1565 children, classified into three groups: seven studies compared high-flow nasal cannula to noninvasive ventilation techniques, four studies compared high-flow nasal cannula to conventional oxygen therapy, and one observational single-arm study explored the use of high-flow nasal cannula with no control group. There was no significant difference in the incidence of tracheal reintubation between high-flow nasal cannula and conventional oxygen therapy (risk ratio [RR] = 0.67, 95% confidence interval [CI]: 0.24-1.90, p = .46). However, there was a lower incidence of tracheal reintubation in patients who were extubated to high-flow nasal cannula versus those extubated to noninvasive ventilation techniques (RR = 0.45, 95% CI: 0.32-0.63, p < .01). The high-flow nasal cannula group also demonstrated a lower mortality rate compared to the noninvasive ventilation techniques group (RR = 0.31, 95% CI: 0.16-0.61, p < .01) as well as a shorter postoperative length of stay (mean difference = -8.76 days, 95% CI: -13.08 to -4.45, p < .01) and shorter intensive care length of stay (mean difference = -4.63 days, 95% CI: -9.16 to -0.11, p = .04). CONCLUSION: High-flow nasal cannula is more effective in reducing the rate of postextubation failure compared to other forms of noninvasive ventilation techniques following surgery for congenital heart disease in pediatric-aged patients. high-flow nasal cannula is also associated with lower mortality rates and shorter length of stay. However, when comparing high-flow nasal cannula to conventional oxygen therapy, the findings were inconclusive primarily due to a limited number of scientific studies available on this specific comparison. Future study is needed to further define the benefit of high-flow nasal cannula compared to conventional oxygen therapy and various types of noninvasive ventilation techniques.

A non-invasive continuous and real-time volumetric monitoring in spontaneous breathing subjects based on bioimpedance-ExSpiron®Xi: a validation study in healthy volunteers.

Tidal volume (TV) monitoring breath-by-breath is not available at bedside in non-intubated patients. However, TV monitoring may be useful to evaluate the work of breathing. A non-invasive device based on bioimpedance provides continuous and real-time volumetric tidal estimation during spontaneous breathing. We performed a prospective study in healthy volunteers aimed at evaluating the accuracy, the precision and the trending ability of measurements of ExSpiron®Xi as compared with the gold standard (i.e. spirometry). Further, we explored whether the differences between the 2 devices would be improved by the calibration of ExSpiron®Xi with a pre-determined tidal volume. Analysis accounted for the repeated nature of measurements within each subject. We enrolled 13 healthy volunteers, including 5 men and 8 women. Tidal volume, TV/ideal body weight (IBW) and respiratory rate (RR) measured with spirometer (TVSpirometer) and with ExSpiron®Xi (TVExSpiron) showed a robust correlation, while minute ventilation (MV) showed a weak correlation, in both non/calibrated and calibrated steps. The analysis of the agreement showed that non-calibrated TVExSpiron underestimated TVspirometer, while in the calibrated steps, TVExSpiron overestimated TVspirometer. The calibration procedure did not reduce the average absolute difference (error) between TVSpirometer and TVExSpiron. This happened similarly for TV/IBW and MV, while RR showed high accuracy and precision. The trending ability was excellent for TV, TV/IBW and RR. The concordance rate (CR) was >95% in both calibrated and non-calibrated measurements. The trending ability of minute ventilation was limited. Absolute error for both calibrated and not calibrated values of TV, TV/IBW and MV accounting for repeated measurements was variably associated with BMI, height and smoking status. Conclusions: Non-invasive TV, TV/IBW and RR estimation by ExSpiron®Xi was strongly correlated with tidal ventilation according to the gold standard spirometer technique. This data was not confirmed for MV. The calibration of the device did not improve its performance. Although the accuracy of ExSpiron®Xi was mild and the precision was limited for TV, TV/IBW and MV, the trending ability of the device was strong specifically for TV, TV/IBW and RR. This makes ExSpiron®Xi a non-invasive monitoring system that may detect real-time tidal volume ventilation changes and then suggest the need to better optimize the patient ventilatory support.

Comparison of BAP65, DECAF, PEARL, and MEWS Scores in Predicting Respiratory Support Need in Hospitalized Exacerbation of Chronic Obstructive Lung Disease Patients.

OBJECTIVE: Prognostic models aid clinical practice with decision-making on treatment and hospitalization in exacerbation of chronic obstructive lung disease (ECOPD). Although there are many studies with prognostic models, diagnostic accuracy is variable within and between models. SUBJECTS AND METHODS: We compared the prognostic performance of the BAP65 score, DECAF score, PEARL score, and modified early warning score (MEWS) in hospitalized patients with ECOPD, to estimate ventilatory support need. RESULTS: This cross-sectional study consisted of 139 patients. Patients in need of noninvasive or invasive mechanical ventilation support are grouped as ventilatory support groups (n = 54). Comparison between receiver operating characteristic curves revealed that the DECAF score is significantly superior to the PEARL score (p = 0.04) in discriminating patients in need of ventilatory support. DECAF score with a cutoff value of 1 presented the highest sensitivity and BAP65 score with a cutoff value of 2 presented the highest specificity in predicting ventilatory support need. Multivariable analysis revealed that gender played a significant role in COPD exacerbation outcome, and arterial pCO2 and RDW measurements were also predictors of ventilatory support need. Within severity indexes, only the DECAF score was independently associated with the outcome. One-point increase in DECAF score created a 1.43 times higher risk of ventilatory support need. All severity indexes showed a correlation with age, comorbidity index, and dyspnea. BAP65 and DECAF scores also showed a correlation with length of stay. CONCLUSION: Objective and practical classifications are needed by clinicians to assess prognosis and initiate treatment accordingly. DECAF score is a strong candidate among severity indexes.

Customized Silicone Foam Dressing Under Noninvasive Ventilation and Skincare Bundle to Reduce Hospital-Acquired Pressure Injuries in Neonates.

In a sixty-eight-bed level-IV NICU, an increased incidence of hospital-acquired pressure injuries (HAPIs) from noninvasive ventilation (NIV) devices was identified. The aim of this quality improvement project was to decrease HAPIs from NIV by 10%. A literature review and the Plan-Do-Study-Act were implemented. The intervention included a customized silicone foam dressing under NIV, an NIV skincare bundle, and multidisciplinary support. Hospital-acquired pressure injury rates were tracked over 3 years postinterventions. The incidence of HAPIs declined by 20% from 0.2 per 1,000 patient days to 0.05 per 1,000 patient days. Relative risk was 4.6 times greater prior to intervention (p = .04). Continuous positive airway pressure (CPAP) failure was not noted and measured by the percentage of patients on ventilators pre- and postintervention. Customized silicone foam dressings under NIV, NIV skincare bundle, and multidisciplinary team support may decrease HAPIs in neonates without CPAP failure.

Clinical characteristics and disease course before and after SARS-CoV-2 infection in a large cohort of systemic sclerosis patients.

Background/aim: The objective of this study is to evaluate the clinical presentations and adverse outcomes of Coronavirus Disease 2019 (COVID-19) in patients with systemic sclerosis (SSc) and assess the impact of SSc features on the clinical course of COVID-19. Materials and methods: In this multicenter, retrospective study, SSc patients with COVID-19 were included. Clinical features of SSc, along with detailed COVID-19 data, were extracted from medical records and patient interviews. Results: The study included 112 patients (mean age 51.4 ± 12.8 years; 90.2% female). SSc-associated interstitial lung disease (ILD) was evident in 57.1% of the patients. The findings revealed hospitalization in 25.5%, respiratory support in 16.3%, intensive care unit admission in 3.6%, and a mortality rate of 2.7% among SSc patients with COVID-19. Risk factors for respiratory failure, identified through univariate analysis, included ILD (OR: 7.49, 95% CI: 1.63-34.46), ≥1 comorbidity (OR: 4.55, 95% CI: 1.39-14.88), a higher physician global assessment score at the last outpatient visit (OR 2.73, 95% CI: 1.22-6.10), and the use of mycophenolate at the time of infection (OR: 5.16, 95 %CI: 1.79-14.99). Notably, ≥1 comorbidity emerged as the sole significant predictor of the need for respiratory support in COVID-19 (OR: 5.78, 95% CI: 1.14-29.23). In the early post-COVID-19 period, 17% of patients reported the progression of the Raynaud phenomenon, and 10.6% developed new digital ulcers. Furthermore, progression or new onset of dyspnea and cough were detected in 28.3% and 11.4% of patients, respectively. Conclusion: This study suggests a potential association between adverse outcomes of COVID-19 and SSc-related ILD, severe disease activity, and the use of mycophenolate. Additionally, it highlights that having comorbidities is an independent risk factor for the need for respiratory support in COVID-19 cases.

[Association Between Different Modes of Respiratory Support and Feeding Intolerance in Preterm Infants: A Retrospective Cohort Study]. / æ—©äº§å„¿å‘¼å¸æ”¯æŒæ¨¡å¼ä¸Žå–‚å »ä¸è€å—çš„å ³ç³»ï¼šä¸€é¡¹å›žé¡¾æ€§é˜Ÿåˆ—ç ”ç©¶.

Objective: To explore the relationship between different modes of respiratory support and feeding intolerance (FI) in preterm infants over the course of their hospitalization and to provide recommendations for the management of enteral feeding in preterm infants requiring respiratory support. Methods: A retrospective analysis was performed with the preterm infants admitted to the Neonatal Intensive Care Unit (NICU), West China Second University Hospital, Sichuan University between June 2015 and November 2018. The modes of respiratory support were used as independent variables and FI was used as the outcome indicator. The preterm infants were grouped according to the specific modes of respiratory support they were on over the course of their hospitalization and the relationship between each mode of respiratory support and FI was compared. Results: A total of 272 preterm infants were enrolled in the study. After adjusting for confounding factors, findings from logistics regression suggested that, compared with normobaric oxygen, high flow nasal cannula (HFNC) might reduce the incidence of FI (odds ratio [OR]=0.53, 95% confidence interval [CI]: 0.06-4.77), while other modes of respiratory support might increase the incidence of FI. Compared with nasal continuous positive airway pressure (NCPAP), bilevel positive airway pressure (BIPAP) and invasive ventilation might increase the incidence of FI, with the adjusted OR being 1.31 and 1.69, and 95% CI being 0.67-2.55 and 0.65-4.41, respectively. The incidence of FI in BIPAP and invasive ventilation was similar (adjusted OR=1.00, 95% CI: 0.41-2.42). However, the P-values of the above results were all greater than 0.05. Conclusion: HFNC has the lowest incidence of FI in the respiratory support modes examined in this study. Attention should be paid to enteral feeding management when using NCPAP, BIPAP, and invasive ventilation to avoid the occurrence of FI. Given the limited sample size, further research is warranted to confirm the conclusion.

IS FLEXIBLE BRONCHOSCOPY A SAFE PROCEDURE FOR CRITICAL CARE PATIENTS WITH RESPIRATORY FAILURE?

Flexible bronchoscopy (FB) plays an important role in critical care patients. But, critical care patients with respiratory failure are at an increased risk of developing complications. Considering the developments in intensive care unit care in recent years, we aimed to evaluate the use of FB in these patients. We retrospectively reviewed patients who underwent FB in critical care between 2014 and 2020. A total of 143 patients underwent FB during the study period. Arterial blood gas measurement on the FB day revealed a mean PaO2/FiO2 of 186.94±28.47. Eighty-one (56.6%) patients underwent an fiberoptic bronchoscopy procedure under conventional oxygen supplementation, 10 (7%) on noninvasive ventilation, 13 (9.1%) on high flow nasal cannula, and 39 (27.3%) on invasive mechanical ventilation. During and immediately after bronchoscopy, none of the patients experienced life-threatening complications. Fifty-five (38.5%) patients developed complications that could be controlled. Multivariate analysis indicated that increased Apache-II score and presence of cardiovascular disease were significantly associated with an increased complication risk. Although critical care patients with respiratory failure are more prone to complications, diagnostic and therapeutic bronchoscopy may be performed following appropriate patient selection, without leading to major complications.

NONINVASIVE MECHANICAL VENTILATION IN COVID-19 RELATED ACUTE RESPIRATORY FAILURE.

Coronavirus disease 2019 (COVID-19) is presented with a wide range of symptoms, from asymptomatic disease to severe and progressive interstitial pneumonia. As part of interstitial pneumonia, respiratory failure is typically presented as hypoxia and is the most common cause of hospitalization. When oxygen therapy fails, continuous positive airway pressure (CPAP) or noninvasive mechanical ventilation (NIV) are used as respiratory support measures of first choice. Noninvasive respiratory support (NIRS) is applied in order to save intensive care unit resources and to avoid complications related to invasive mechanical ventilation. Emerging evidence has shown that the use of CPAP or NIV in the management of acute hypoxemic respiratory failure in COVID-19 reduces the need for intubation and mortality. The advantage of NIRS is the feasibility of its application on wards. NIV could be administered via a face mask or helmet interface. Helmet adheres better than mask and therefore leakage is reduced, a delivery of positive end-expiratory pressure is more accurate, and the risk of nosocomial transmission of infections is lowered. Patients on NIRS must be carefully monitored so that further respiratory deterioration is not overlooked and additional measures of care including timely intubation and invasive mechanical ventilation could be performed if needed.

High-flow nasal oxygen in infants and children for early respiratory management of pneumonia-induced acute hypoxemic respiratory failure: the CENTURI randomized clinical trial.

Objective: To compare the effectiveness of early high-flow nasal cannula (HFNC) and low-flow oxygen support (LFOS) in children under 5 years with acute hypoxemic respiratory failure (AHRF) due to severe community-acquired pneumonia in low-middle-income countries. Methods: An open-label randomized clinical trial enrolled children aged 2-59 months with AHRF due to severe community-acquired pneumonia and randomized into HFNC and LFOS. In the LFOS group, the patient received cold wall oxygen humidified by bubbling through sterile water administered through simple nasal prongs at a fixed flow rate of 2 L/min. In the HFNC group, the patient received humidified, heated (37 °C), high-flow oxygen at a flow rate assigned based on weight range, with a titratable oxygen fraction. The primary outcome was treatment failure in 72 h (escalating the respiratory support method using any modality other than primary intervention). Results: Data was analyzed intention-to-treat (HFNC = 124; LFOS = 120). Median (IQR) age was 12 (6-20) and 11 (6-27) months, respectively. Treatment failure occurred in a significantly lower proportion in the HFNC group (7.3%, n = 9/124) as compared to the LFOS group (20%, n = 24/120) (relative risk = 0.36, 95% CI 0.18 to 0.75; p = 0.004; adjusted hazard ratio 0.34, 95% CI 0.16 to 0.73; p = 0.006). The intubation rate was significantly lower in the HFNC group (7.3%, n = 9/124 vs. 16.7%, n = 20/120; relative risk = 0.44, 95% CI 0.21 to 0.92, p = 0.023). There were no significant differences noted in other secondary outcomes. No mortality occurred. Conclusion: High-flow nasal cannula oxygen therapy used as early respiratory support in children under 5 years with acute hypoxemic respiratory failure due to severe community-acquired pneumonia was associated with significantly lower treatment failure compared with standard low-flow oxygen support. Trial registration: CTRI/2016/04/006788. Registered 01 April 2016, https://ctri.nic.in/Clinicaltrials/advsearch.php. Supplementary Information: The online version contains supplementary material available at 10.1007/s44253-024-00031-8.

The developmental phenotype of motor delay in extremely preterm infants following early-life respiratory adversity is influenced by brain dysmaturation in the parietal lobe.

BACKGROUND: Research indicates that preterm infants requiring prolonged mechanical ventilation often exhibit suboptimal neurodevelopment at follow-up, coupled with altered brain development as detected by magnetic resonance imaging (MRI) at term-equivalent age (TEA). However, specific regions of brain dysmaturation and the subsequent neurodevelopmental phenotype following early-life adverse respiratory exposures remain unclear. Additionally, it is uncertain whether brain dysmaturation mediates neurodevelopmental outcomes after respiratory adversity. This study aims to investigate the relationship between early-life adverse respiratory exposures, brain dysmaturation at TEA, and the developmental phenotype observed during follow-up in extremely preterm infants. METHODS: 89 infants born < 29 weeks' gestation from 2019 to 2021 received MRI examinations at TEA for structural and lobe brain volumes, which were adjusted with sex-and-postmenstrual-age expected volumes for volume residuals. Assisted ventilation patterns in the first 8 postnatal weeks were analyzed using kmlShape analyses. Patterns for motor, cognition, and language development were evaluated from corrected age 6 to 12 months using Bayley Scales of Infant Development, third edition. Mediation effects of brain volumes between early-life respiratory exposures and neurodevelopmental phenotypes were adjusted for sex, gestational age, maternal education, and severe brain injury. RESULTS: Two distinct respiratory trajectories with varying severity were identified: improving (n = 35, 39%) and delayed improvement (n = 54, 61%). Compared with the improving group, the delayed improvement group exhibited selectively reduced brain volume residuals in the parietal lobe (mean - 4.9 cm3, 95% confidence interval - 9.4 to - 0.3) at TEA and lower motor composite scores (- 8.7, - 14.2 to - 3.1) at corrected age 12 months. The association between delayed respiratory improvement and inferior motor performance (total effect - 8.7, - 14.8 to - 3.3) was partially mediated through reduced parietal lobe volume (natural indirect effect - 1.8, - 4.9 to - 0.01), suggesting a mediating effect of 20%. CONCLUSIONS: Early-life adverse respiratory exposure is specifically linked to the parietal lobe dysmaturation and neurodevelopmental phenotype of motor delay at follow-up. Dysmaturation of the parietal lobe serves as a mediator in the connection between respiratory adversity and compromised motor development. Optimizing respiratory critical care may emerge as a potential avenue to mitigate the consequences of altered brain growth and motor developmental delay in this extremely preterm population.

Non-Invasive Ventilatory Support in Preterm Neonates in the Delivery Room and the Neonatal Intensive Care Unit: A Short Narrative Review of What We Know in 2024.

BACKGROUND: Guidelines recommend non-invasive ventilatory (NIV) support as first-line respiratory support mode in preterm infants as NIV is superior to intubation and mechanical ventilation in preventing death or bronchopulmonary dysplasia. However, with an ever-expanding variety of NIV modes available, there is much debate about which NIV modality should ideally be used, how, and when. The aims of this work were to summarise the evidence on different NIV modalities for both primary and secondary respiratory support: nCPAP, nasal high-flow therapy (nHFT), and nasal intermittent positive airway pressure ventilation (nIPPV), bi-level positive airway pressure (BiPAP), nasal high-frequency oscillatory ventilation (nHFOV), and nasally applied, non-invasive neurally adjusted ventilatory assist (NIV-NAVA) modes, with particular focus on their use in preterm infants. SUMMARY: This is a narrative review with reference to published guidelines by European Consensus Guidelines on the Management of Respiratory Distress Syndrome: 2022 Update. nCPAP is currently the most commonly used primary and secondary NIV modality for premature infants. However, there is increasing evidence on the superiority of nIPPV over nCPAP. No beneficial effect was found for BiPAP over nCPAP. For the use of nHFT, nHFOV, and NIV-NAVA, more studies are needed to establish their place in neonatal respiratory care. KEY MESSAGES: The superiority of nIPPV over nCPAP needs to be confirmed by contemporaneous trials comparing nCPAP to nIPPV at comparable mean airway pressures. Future trials should study NIV modalities in preterm infants with comparable respiratory pathology and indications, at comparable pressure settings and with different modes of synchronisation. Importantly, future trials should not exclude infants of the smallest gestational ages.

Veno-arterial extracorporeal membrane oxygenation for respiratory and cardiac support in neonates: a single center experience.

Objective: Extracorporeal membrane oxygenation (ECMO) is an advanced life support that has been utilized in the neonate for refractory respiratory and circulatory failure. Striving for the best outcomes and understanding optimal surgical techniques continue to be at the forefront of discussion and research. This study presents a single-center experience of cervically cannulated neonatal patients on V-A ECMO, a description of our cannulation/decannulation techniques and our patient outcomes. Methods: Single center retrospective review of neonates who received neck V-A ECMO support from January 2012 to December 2022. The data and outcomes of the patients were retrospectively analyzed. Results: A total of 78 neonates received V-A ECMO support. There were 66 patients that received ECMO for respiratory support, the other 12 patients that received ECMO for cardiac support. The median duration of ECMO support was 109 (32-293) hours for all patients. During ECMO support, 20 patients died and 5 patients discontinued treatment due to poor outcome or the cost. A total of 53 (68%) patients were successfully weaned from ECMO, but 3 of them died in the subsequent treatment. Overall 50 (64%) patients survived to hospital discharge. In this study, 48 patients were cannulated using the vessel sparing technique, the other 30 patients were cannulated using the ligation technique. We found no significant difference in the rates of normal cranial MRI at discharge between survivors with and without common carotid artery ligation. Conclusion: We achieved satisfactory outcomes of neonatal ECMO in 11-year experience. This study found no significant difference in early neuroimaging between survivors with and without common carotid artery ligation. The long-term neurological function of ECMO survivors warranted further follow-up and study.

Pneumomediastinum and pneumothorax in coronavirus disease-2019: Description of a case series and a matched cohort study.

Objective: To describe the characteristics of COVID-19 patients with pneumothorax and pneumomediastinum (PTX/PM) and their association with patient outcomes. Patients and methods: Adults admitted to five Mayo Clinic hospitals with COVID-19 between 03/2020-01/2022 were evaluated. PTX/PM was defined by imaging. Descriptive analyses and a matched (age, sex, admission month, COVID-19 severity) cohort comparison was performed. Hospital mortality, length of stay (LOS), and predisposing factors were assessed. Results: Among 6663 patients, 197 had PTX/PM (3 %) (75 PM, 40 PTX, 82 both). The median age was 59, with 71 % males. Exposure to invasive and non-invasive mechanical ventilation and high-flow nasal cannula before PTX/PM were 42 %, 17 %, and 20 %, respectively. Among isolated PTX and PM/PTX patients 70 % and 53.7 % underwent an intervention, respectively, while 96 % of the PM-only group was followed conservatively.A total of 171 patients with PTX/PM were compared to 171 matched controls. PTX/PM patients had more underlying lung disease (40.9 vs. 23.4 %, p < 0.001) and lower median body mass index (BMI) (29.5 vs. 31.3 kg/m2, p = .007) than controls. Among patients with available data, PTX/PM patients had higher median positive end-expiratory and plateau pressures than controls; however, differences were not significant (10 vs. 8 cmH2O; p = 0.38 and 28 vs. 22 cmH2O; p = 0.11, respectively). PTX/PM patients had a higher odds of mortality (adjusted odds ratio [95%CI]: 3.37 [1.61-7.07]) and longer mean LOS (percent change [95%CI]: 39 [9-77]) than controls. Conclusion: In COVID-19 patients with similar severity, PTX/PM patients had more underlying lung disease and lower BMI. They had significantly increased mortality and LOS.

Outcomes of critically ill patients with liver failure who require mechanical ventilation: A retrospective, single-center study.

Background and Aims: Critically ill patients with liver failure have high mortality. Besides the management of organ-specific complications, liver transplantation constitutes a definitive treatment. However, clinicians may hesitate to introduce mechanical ventilation for patients on liver transplantation waitlists because of poor prognosis. This study investigated the outcomes of intensive care and ventilation support therapy effects in patients with liver failure. Methods: This single-center study retrospectively enrolled 32 consecutive patients with liver failure who were admitted to the intensive care unit from January 2014 to December 2020. The medical records were reviewed and analyzed retrospectively for Acute Physiologic and Chronic Health Evaluation (APACHE)-II. The model for end-stage liver disease scores, 90-day mortality, and survival was assessed using the Kaplan-Meier method. Results: The average patient age was 45.5 ± 20.1 years, and 53% of patients were women. On intensive care unit admission, APACHE-II and model for end-stage liver disease scores were 20 and 28, respectively. Among 13 patients considered for liver transplantation, 4 received transplants. Thirteen patients (40.6%) were intubated and mechanically ventilated in the intensive care unit. The 90-day mortality rate of patients with and without mechanical ventilation in the intensive care unit (13, 61.5% vs. 19, 47.4%, p = 0.4905) was similar. APACHE-II score >21 was an independent predictor of mechanical ventilation requirement in patients with liver failure during intensive care unit stay. Conclusion: Although critically ill patients with liver failure are at risk of multiorgan failure with poor outcomes, mechanical ventilation did not negatively affect the 90-day mortality or performance rates of liver transplantation. Clinicians should consider mechanical ventilation-based life support in critically ill patients with liver failure who are awaiting liver transplantation.

Institutional Variability in Respiratory Support Use for Pediatric Critical Asthma: A Multicenter Retrospective Study.

Rationale: Over 20,000 children are hospitalized in the United States for asthma every year. Although initial treatment guidelines are well established, there is a lack of high-quality evidence regarding the optimal respiratory support devices for these patients.Objectives: The objective of this study was to evaluate institutional and temporal variability in the use of respiratory support modalities for pediatric critical asthma.Methods: We conducted a retrospective cohort study using data from the Virtual Pediatrics Systems database. Our study population included children older than 2 years old admitted to a VPS contributing pediatric intensive care unit from January 2012 to December 2021 with a primary diagnosis of asthma or status asthmaticus. We evaluated the percentage of encounters using a high-flow nasal cannula (HFNC), continuous positive airway pressure (CPAP), noninvasive bilevel positive pressure ventilation (NIV), and invasive mechanical ventilation (IMV) for all institutions, then divided institutions into quintiles based on the volume of patients. We created logistic regression models to determine the influence of institutional volume and year of admission on respiratory support modality use. We also conducted time-series analyses using Kendall's tau.Results: Our population included 77,115 patient encounters from 163 separate institutions. Institutional use of respiratory modalities had significant variation in HFNC (28.3%, interquartile range [IQR], 11.0-49.0%; P < 0.01), CPAP (1.4%; IQR, 0.3-4.3%; P < 0.01), NIV (8.6%; IQR, 3.5-16.1%; P < 0.01), and IMV (5.1%; IQR, 3.1-8.2%; P < 0.01). Increased institutional patient volume was associated with significantly increased use of NIV (odds ratio [OR], 1.33; 1.29-1.36; P < 0.01) and CPAP (OR, 1.20; 1.15-1.25; P < 0.01), and significantly decreased use of HFNC (OR, 0.80; 0.79-0.81; P < 0.01) and IMV (OR, 0.82; 0.79-0.86; P < 0.01). Time was also associated with a significant increase in the use of HFNC (11.0-52.3%; P < 0.01), CPAP (1.6-5.4%; P < 0.01), and NIV (3.7-21.2%; P < 0.01), whereas there was no significant change in IMV use (6.1-4.0%; P = 0.11).Conclusions: Higher-volume centers are using noninvasive positive pressure ventilation more frequently for pediatric critical asthma and lower frequencies of HFNC and IMV. Treatment with HFNC, CPAP, and NIV for this population is increasing in the last decade.

Association of Fluid Overload with Escalation of Respiratory Support and Endotracheal Intubation in Acute Bronchiolitis Patients.

Fluid overload has been associated with increased oxygen requirement, prolonged duration of mechanical ventilation, and longer length of hospital stay in children hospitalized with pulmonary diseases. Critically ill infants with bronchiolitis admitted to the pediatric intensive care unit (PICU) also tend to develop fluid overload and there is limited information of its role on noninvasive respiratory support. Thus, our primary objective was to study the association of fluid overload in patients with bronchiolitis admitted to the PICU with respiratory support escalation (RSE) and need for endotracheal intubation (ETI). Infants ≤24 months of age with bronchiolitis and admitted to the PICU between 9/2009 and 6/2015 were retrospectively studied. Demographic variables, clinical characteristics including type of respiratory support and need for ETI were evaluated. Fluid overload as assessed by net fluid intake and output (net fluid balance), cumulative fluid balance (CFB) (mL/kg), and percentage fluid overload (FO%), was compared between patients requiring and not requiring RSE and among patients requiring ETI and not requiring ETI at 0 (PICU admission), 12, 24, 36, 48, 72, 96, and 120 hours. One-hundred sixty four of 283 patients with bronchiolitis admitted to the PICU qualified for our study. Thirty-four of 164 (21%) patients required escalation of respiratory support within 5 days of PICU admission and of these 34 patients, 11 patients required ETI. Univariate analysis by Kruskal-Wallis test of fluid overload as assessed by net fluid balance, CFB, and FO% between 34 patients requiring and 130 patients not requiring RSE and among 11 patients requiring ETI and 153 patients not requiring ETI, at 0, 12, 24, 36, 48, 72, 96 and 120 hours did not reveal any significant difference ( p >0.05) at any time interval. Multivariable logistic regression analysis revealed higher PRISM score (odds ratio [OR]: 4.95, 95% confidence interval [95% CI]: 1.79-13.66; p = 0.002), longer hours on high flow nasal cannula (OR: 4.86, 95% CI: 1.68-14.03; p = 0.003) and longer hours on noninvasive ventilation (OR: 11.16, 95% CI: 3.36-36.98; p < 0.001) were associated with RSE. Fluid overload as assessed by net fluid balance, CFB, and FO% was not associated with RSE or need for ETI in critically ill bronchiolitis patients admitted to the PICU. Further prospective studies involving larger number of patients with bronchiolitis are needed to corroborate our findings.