Lung ultrasound-guided fluid resuscitation in neonatal septic shock: A randomized controlled trial.

This randomized controlled trial aimed to determine whether lung ultrasound-guided fluid resuscitation improves the clinical outcomes of neonates with septic shock. Seventy-two patients were randomly assigned to undergo treatment with lung ultrasound-guided fluid resuscitation (LUGFR), or with usual fluid resuscitation (Control) in the first 6 h since the start of the sepsis treatment. The primary study outcome was 14-day mortality after randomization. Fourteen-day mortalities in the two groups were not significantly different (LUGFR group, 13.89%; control group, 16.67%; p = 0.76; hazard ratio 0.81 [95% CI 0.27-2.50]). The LUGFR group experienced shorter length of neonatal intensive care unit (NICU) stays (21 vs. 26 days, p = 0.04) and hospital stays (32 vs. 39 days, p = 0.01), and less fluid was used in the first 6 h (77 vs. 106 mL/kg, p = 0.02). Further, our study found that ultrasound-guided fluid resuscitation can significantly reduce the incidence of acute kidney injury (25% vs. 47.2%, p = 0.05) and intracranial hemorrhage (grades I-II) within 72 h (13.9% vs. 36.1%, p = 0.03). However, no significant difference was found in the resolution of shock within 1 h or 6 h, use of mechanical ventilation or vasopressor support, time to achieve lactate level < 2 mmol/L, and the number of participants developing hepatomegaly in the first 6 h. CONCLUSION: Lung ultrasound is a noninvasive and convenient tool for predicting fluid overload in neonatal septic shock. Fluid resuscitation guided by lung ultrasound can shorten the length of hospital and NICU stays, reduce the amount of fluid used in the first 6 h, and reduce the risk of acute kidney injury and intracranial hemorrhage. TRIAL REGISTRATION: Registered in Guangdong Second Provincial General Hospital: 2021-IIT-156-EK, date of registration: November 13, 2021. And ClinicalTrials.gov: NCT06144463 (retrospectively registered). WHAT IS KNOWN: • Excessive fluid resuscitation in neonates with septic shock had worse outcomes. WHAT IS NEW: • Lung ultrasound should be routinely used to guide fluid resuscitation in neonatal septic shock.

Short term outcomes of extremely low birth weight infants from a multicenter cohort study in Guangdong of China.

With the increase in extremely low birth weight (ELBW) infants, their outcome attracted worldwide attention. However, in China, the related studies are rare. The hospitalized records of ELBW infants discharged from twenty-six neonatal intensive care units in Guangdong Province of China during 2008-2017 were analyzed. A total of 2575 ELBW infants were enrolled and the overall survival rate was 55.11%. From 2008 to 2017, the number of ELBW infants increased rapidly from 91 to 466, and the survival rate improved steadily from 41.76% to 62.02%. Increased survival is closely related to birth weight (BW), regional economic development, and specialized hospital. The incidence of complications was neonatal respiratory distress syndrome (85.2%), oxygen dependency at 28 days (63.7%), retinopathy of prematurity (39.3%), intraventricular hemorrhage (29.4%), necrotizing enterocolitis (12.0%), and periventricular leukomalacia (8.0%). Among the 1156 nonsurvivors, 90.0% of infants died during the neonatal period (≤ 28 days). A total of 768 ELBW infants died after treatment withdrawal, for reasons of economic and/or poor outcome. The number of ELBW infants is increasing in Guangdong Province of China, and the overall survival rate is improving steadily.

Three exposure metrics of size-specific particulate matter associated with acute lower respiratory infection hospitalization in children: A multi-city time-series analysis in China.

BACKGROUND: The global burden of acute lower respiratory infection (ALRI) attributable to air pollution has increased in recent years, but the association between ALRI and exposure to size-specific particulate matter has not been investigated using different exposure metrics. METHODS: We obtained ALRI admission from seven cities from 2014 to 2016 in China. Different sized particles were measured using three metrics (a) daily mean, (b) hourly peak, and (c) daily excessive concentration hours (DECH). Generalized additive models were fitted for each of the seven cities, and the city-specific estimates were then pooled using random-effects meta-analysis models. Stratified analyses were conducted to examine the effect modifications of gender, age, and season. We also estimated the disease burden due to particulate matter exposures. RESULTS: There were 111,426 ALRI (79,803 pneumonia and 31,622 bronchiolitis) hospital admissions under the age of 15 between 2014 and 2016 in our study. Daily means were associated with the largest ALRI estimates (95% confidence interval [CI]): 2.43% (0.79%, 4.11%) for PM2.5, 2.25% (0.11%, 4.44%) for PMc, and 2.64% (0.73%, 4.58%) for PM10. The magnitude of effect sizes were followed by DECH: 1.94% (0.51%, 3.39%) for PM2.5, 0.88% (-0.14%, 1.92%) for PMc, 1.86% (0.50%, 2.01%) for PM10; and hourly peak: 0.70% (-0.60%, 2.01%) for PM2.5, 1.05% (-0.13%, 2.66%) for PMc, and 1.20% (-0.20%, 2.62%) for PM10 at lag03. We found significantly higher effects in cold seasons than that in warm seasons, while we did not find a significant different between gender and age groups. CONCLUSIONS: The adverse effects of exposure to particulate matter on ALRI hospitalizations are reconfirmed. DECH was a possible alternative exposure indicator for PM2.5 assessment, which may affect air quality standards in the future.

Size-Specific Particulate Matter Associated With Acute Lower Respiratory Infection Outpatient Visits in Children: A Counterfactual Analysis in Guangzhou, China.

The burden of lower respiratory infections is primarily evident in the developing countries. However, the association between size-specific particulate matter and acute lower respiratory infection (ALRI) outpatient visits in the developing countries has been less studied. We obtained data on ALRI outpatient visits (N = 105,639) from a tertiary hospital in Guangzhou, China between 2013 and 2019. Over-dispersed generalized additive Poisson models were employed to evaluate the excess risk (ER) associated with the size-specific particulate matter, such as inhalable particulate matter (PM10), coarse particulate matter (PMc), and fine particulate matter (PM2.5). Counterfactual analyses were used to examine the potential percent reduction of ALRI outpatient visits if the levels of air pollution recommended by the WHO were followed. There were 35,310 pneumonia, 68,218 bronchiolitis, and 2,111 asthma outpatient visits included. Each 10 µg/m3 increase of 3-day moving averages of particulate matter was associated with a significant ER (95% CI) of outpatient visits of pneumonia (PM2.5: 3.71% [2.91, 4.52%]; PMc: 9.19% [6.94, 11.49%]; PM10: 4.36% [3.21, 5.52%]), bronchiolitis (PM2.5: 3.21% [2.49, 3.93%]; PMc: 9.13% [7.09, 11.21%]; PM10: 3.12% [2.10, 4.15%]), and asthma (PM2.5: 3.45% [1.18, 5.78%]; PMc: 11.69% [4.45, 19.43%]; PM10: 3.33% [0.26, 6.49%]). The association between particulate matter and pneumonia outpatient visits was more evident in men patients and in the cold seasons. Counterfactual analyses showed that PM2.5 was associated with a larger potential decline of ALRI outpatient visits compared with PMc and PM10 (pneumonia: 11.07%, 95% CI: [7.99, 14.30%]; bronchiolitis: 6.30% [4.17, 8.53%]; asthma: 8.14% [2.65, 14.33%]) if the air pollutants were diminished to the level of the reference guidelines. In conclusion, short-term exposures to PM2.5, PMc, and PM10 are associated with ALRI outpatient visits, and PM2.5 is associated with the highest potential decline in outpatient visits if it could be reduced to the levels recommended by the WHO.

Roles of Lung Ultrasound Score in the Extubation Failure From Mechanical Ventilation Among Premature Infants With Neonatal Respiratory Distress Syndrome.

Objective: To investigate the predictive value of lung ultrasound score (LUS) in the extubation failure from mechanical ventilation (MV) among premature infants with neonatal respiratory distress syndrome (RDS). Methods: The retrospective cohort study was conducted with a total of 314 RDS newborns who received MV support for over 24 h. After extubation from MV, infants were divided into extubation success and extubation failure groups. Extubation failure was defined as re-intubation within 48 h after extubation. Univariate and multivariate logistic regression analyses were used to identify the predictors of the extubation failure. The predictive effectiveness of the combined model and LUS in the extubation failure was assessed by receiver operating characteristic curve, area under curve (AUC), and internal validation. Results: 106 infants failed extubation from MV. The combined model for predicting the extubation failure was performed according to the predictors of gestational age, body length, birth weight, and LUS. The AUC of this combined model was 0.871 (sensitivity: 86.67%, specificity: 74.31%). The AUC of LUS was 0.858 (sensitivity: 84.00%, specificity: 80.69%), and the cutoff value was 18. There was no statistical difference in the predictive power between the combined model and LUS (Z = 0.880, P = 0.379). The internal validation result showed that the AUC of LUS was 0.855. Conclusions: LUS presented a good ability in predicting the extubation failure among RDS newborns after MV.

SEMA3A protects against hyperoxia-induced lung injury in a bronchopulmonary dysplasia model of newborn rat by inhibiting ERK pathway.

BACKGROUND: Hyperoxia induces lung injury through lung inflammation in premature infants, leading to bronchopulmonary dysplasia (BPD). Semaphorin 3A (SEMA3A) participates in diverse biological processes, including cell migration, angiogenesis, and inflammation. The effect of SEMA3A on hyperoxic lung injury of neonatal rats with BPD was investigated in this study. METHODS: Neonatal rats with BPD were established through hyperoxia treatment. Hematoxylin-eosin staining was used to evaluate histopathological analysis in lung tissues. SEMA3A expression was assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot assay. Adeno-associated virus (AAV)-mediated over-expression of SEMA3A (AAV-SEMA3A) was administrated into hyperoxia-induced rats, and apoptosis was evaluated by TUNEL staining. Levels of inflammatory cytokines were investigated by enzyme-linked-immunosorbent serologic assay (ELISA). RESULTS: Hyperoxia-induced histopathological changes in lung tissue reduced alveolar number and enhanced alveolar interval and alveolar volume. SEMA3A was downregulated in lung tissue of hyperoxia-induced rats. AAV-SEMA3A injection attenuated hyperoxia-induced cell apoptosis in lung tissues by increasing Bcl-2 and decreasing Bax and cleaved caspase-3. Moreover, the enhanced levels of Interleukin (IL)-1ß, monocyte chemoattractant protein (MCP)-1, and tumor necrosis factor-α (TNF-α) in hyperoxia-induced rats were restored by AAV-SEMA3A injection by the downregulation of nuclear factor kappa B (NF-κB) phosphorylation. AAV-SEMA3A injection also ameliorated histopathological changes in lung tissues of hyperoxia-induced rats by increasing the number of radial alveolar count and decreasing the volume of mean linear intercept. Besides, the protein expression levels of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) phosphorylation were reduced in hyperoxia-induced rats post-AAV-SEMA3A injection. CONCLUSION: Ectopical expression of SEMA3A suppressed hyperoxia-induced apoptosis and inflammation in neonatal rats, and ameliorated the histopathological changes through inactivation of ERK/JNK pathway.

High frequency oscillatory ventilation versus conventional ventilation in a newborn piglet model with acute lung injury.

BACKGROUND: High frequency oscillatory ventilation (HFOV) is considered a protective strategy for human lungs. This study was designed to define microscopic structural features of lung injury following HFOV with a high lung volume strategy in newborn piglets with acute lung injury. METHODS: After acute lung injury with saline lavage, newborn piglets were randomly assigned to 5 study groups (6 in each group): control (no mechanical ventilation), conventional mechanical ventilation for 24 hours, conventional ventilation for 48 hours, HFOV for 24 hours, and HFOV for 48 hours. The right upper lung tissue was divided into the gravitation-dependent and gravitation-nondependent regions after the completion of mechanical ventilation. Under light microscopy, the numbers of polymorphonuclear leukocytes (PMNLs), alveolar macrophages, red blood cells, and hyaline membrane/alveolar edema were assessed in all lung tissues. Oxygenation index was continuously monitored. RESULTS: Our results showed that the degree of histopathologic lung damage in the gravitation-dependent region was greater than that in the gravitation-nondependent region. Compared with the control group, PMNLs, red blood cells and hyaline membrane/alveolar edemas were significantly increased and alveolar macrophages were significantly decreased in lung tissues of conventional ventilation and HFOV piglets. In HFOV with high lung volume strategy piglets, lung tissues had significantly fewer PMNLs, red blood cells, and hyaline membrane/alveolar edemas, and oxygenation was improved significantly, compared to those of the conventional ventilation piglets. CONCLUSIONS: Histopathologic lung damage in newborn piglets with lung injury was more severe in the gravitation-dependent region than in the gravitation-nondependent region. HFOV with high lung volume strategy reduced pulmonary PMNL infiltration, hemorrhage, alveolar edema, and hyaline membrane formation with improved oxygenation.

Ultrastructural study of alveolar epithelial type II cells by high-frequency oscillatory ventilation.

Alveolar epithelial type II cells (AECIIs) containing lamellar bodies (LBs) are alveolar epithelial stem cells that have important functions in the repair of lung structure and function after lung injury. The ultrastructural changes in AECIIs after high-frequency oscillatory ventilation (HFOV) with a high lung volume strategy or conventional ventilation were evaluated in a newborn piglet model with acute lung injury (ALI). After ALI with saline lavage, newborn piglets were randomly assigned into five study groups (three piglets in each group), namely, control (no mechanical ventilation), conventional ventilation for 24 h, conventional ventilation for 48 h, HFOV for 24 h, and HFOV for 48 h. The lower tissues of the right lung were obtained to observe the AECII ultrastructure. AECIIs with reduced numbers of microvilli, decreased LBs electron density, and vacuole-like LBs deformity were commonly observed in all five groups. Compared with conventional ventilation groups, the decrease in numbers of microvilli and LBs electron density, as well as LBs with vacuole-like appearance and polymorphic deformity, was less severe in HFOV with high lung volume strategy groups. AECIIs were injured during mechanical ventilation. HFOV with a high lung volume strategy resulted in less AECII damage than conventional ventilation.