IntroductionDigital trials are a promising strategy to increase the evidence base for common interventions and may convey considerable efficiency benefits in trial conduct. Although paediatric intensive care units (PICUs) are rich in routine electronic data, highly pragmatic digital trials in this field remain scarce. There are unmet evidence needs for optimal mechanical ventilation modes in paediatric intensive care. We aim to test the feasibility of a digital PICU trial comparing two modes of invasive mechanical ventilation using carbon dioxide (CO2) control as the outcome measure.Methods and analysisSingle-centre, open-labelled, randomised controlled pilot trial with two parallel treatment arms comparing pressure control versus pressure-regulated volume control. Patients are eligible if aged <18 years, weighing >2 kg, have an arterial line and require >60 min of mechanical ventilation during PICU hospitalisation at the University Children’s Hospital Zurich. Exclusion criteria include cardiac shunt lesions, pulmonary hypertension under treatment and intracranial hypertension. CO2is measured using three methods: end-tidal (continuous), transcutaneous (continuous) and blood gas analyses (intermittent). Baseline, intervention and outcome data are collected electronically from the patients’ routine electronic health records. The primary feasibility outcome is adherence to the assigned ventilation mode, while the primary physiological outcome is the proportion of time spent within the target range of CO2(end-tidal, normocarbia defined as CO2≥ 4.5 and ≤ 6 kPa). Both primary outcomes are captured digitally every minute from randomisation until censoring (at 48 hours after randomisation, extubation, discharge or death, whichever comes first). Analysis will occur on an intention-to-treat basis. We aim to enrol 60 patients in total. Recruitment started in January 2024 and continued for 9 months.Ethics and disseminationThis study received ethical approval from the Cantonal Ethics Commission of Zurich (identification number: 2022–00829). Study results will be disseminated through publication in a peer-reviewed journal and other media like podcasts.Trial registration numberNCT05843123.

Antibiotic overtreatment fosters multidrug-resistance that threatens healthcare systems worldwide as it increases patient morbidity and mortality. Contemporary data on antibiotic usage on tertiary care paediatric intensive care units for in- and external benchmarking are scarce. This was a single-centre retrospective quality control study including all patients with antibiotic treatment during their hospitalization at a paediatric intensive care unit in the time period 2019–2021. Antibiotic treatment was calculated as days of therapy (DOT) per 100 patient days (DOT/100pd). Further, the variables PIM II score, length of stay in intensive care (LOS), gender, age, treatment year, reason for intensive care unit admission, and death were assessed. Two thousand and forty-one cases with a median age of 10 months [IQR 0–64] were included; 53.4% were male, and 4.5% of the included patients died. Median LOS was 2.73 days [0.07–5.90], and PIM II score was 1.98% [0.02–4.86]. Overall, the antibiotic exposure of critically ill children and adolescents was 59.8 DOT/100pd. During the study period, the antibiotic usage continuously increased (2019: 55.2 DOT/100pd; 2020: 59.8 DOT/100pd (+8.2%); 2021: 64.5 DOT/100pd (+8.0%)). The highest antibiotic exposure was found in the youngest patients (0–1 month old (72.7 DOT/100pd)), in patients who had a LOS of >2–7 days (65.1 DOT/100pd), those who had a renal diagnosis (98 DOT/100pd), and in case of death (91.5 DOT/100pd). Critically ill paediatric patients were moderately exposed to antibiotics compared to data from the previously published literature. The current underreporting of antimicrobial prescription data in this cohort calls for future studies for better internal and external benchmarking.

Background: Intravenous arginine vasopressin is increasingly used for the treatment of critically ill children. It bears the risk of hyponatraemia with potential severe long-term sequelae, but data on hyponatraemia as a side effect of continuous vasopressin infusion for paediatric intensive care patients is scarce. Methods: In this retrospective analysis performed at a tertiary care paediatric intensive care unit with 2000 annual admissions, patients were included if they were treated with intravenous vasopressin between 2016 and 2022. Baseline sodium concentrations, lowest sodium concentrations during arginine vasopressin treatment, and time to lowest sodium concentration (nadir) were derived. Results: In total, 170 patients with a median age of 4 months [interquartile range, IQR, 0–33] were included, 92.4% underwent surgery, and 28.8% died. Median arginine vasopressin dose rate was 0.027 IU/kg/h [0.019–0.036] and arginine vasopressin was started 3.2 [0–26] h after intensive care admission. Median arginine vasopressin application duration was 13.6 h [6.2–32.6]. Baseline sodium was 141 mmol/L [138–145], and lowest median sodium during arginine vasopressin infusion was 137 mmol/L [132–141] (nadir at 8.4 h [1.0–28.1] after arginine vasopressin start). Hyponatraemia (<135 mmol/L) occurred in 38.2% of patients during AVP treatment, and physicians administered a median of 10.2 mmol/kg/d [6.2–16.4] sodium during arginine vasopressin therapy. Conclusions: Under arginine vasopressin infusion, hyponatraemia was common, although high daily doses of sodium were administered to keep the serum values in physiologic ranges. This emphasises the need for close electrolyte monitoring and sodium substitution in children and adolescents under arginine vasopressin treatment to avoid hyponatraemia and related sequelae.

Neonatal diagnosis of inflammatory bowel disease (IBD) proves challenging due to its non-specific symptoms. A term-born neonate showing states of inflammation and aphthae was treated for sepsis and candidiasis before being diagnosed with interleukin-10 receptor deficiency and consecutive IBD. The patient was finally successfully treated by stem cell transplantation. The case illustrates the difficulties of the diagnostic course in IBD as it may mimic other diseases and emphasizes the importance of considering rare differential diagnoses early in the diagnostic process.

Introduction: Digital trials are a promising strategy to increase the evidence base for common interventions and may convey considerable efficiency benefits in trial conduct. Although paediatric intensive care units (PICUs) are rich in routine electronic data, highly pragmatic digital trials in this field remain scarce. There are unmet evidence needs for optimal mechanical ventilation modes in paediatric intensive care. We aim to test the feasibility of a digital PICU trial comparing two modes of invasive mechanical ventilation using carbon dioxide (CO2) control as the outcome measure. Methods and analysis: Single-centre, open-labelled, randomized controlled pilot trial with two parallel treatment arms comparing pressure control (PC) vs pressure-regulated volume control (PRVC). Patients are eligible if aged <18 years, weighing >2 kg, have an arterial line, and require >60 minutes of mechanical ventilation during PICU hospitalization at the University Children's Hospital Zurich. Exclusion criteria include cardiac shunt lesions, pulmonary hypertension under treatment, and intracranial hypertension. CO2 is measured using three methods: end-tidal (continuous), transcutaneous (continuous), and blood gas analyses (intermittent). Baseline, intervention, and outcome data are collected electronically from the patients' routine electronic health records. The primary feasibility outcome is adherence to the assigned ventilation mode, while the primary physiological outcome is the proportion of time spent within the target range of CO2 (end-tidal, normocarbia defined as CO2 ≥ 4.5, ≤ 6 kPa). Both outcomes are captured digitally every minute from randomization until censoring (48 hours after randomization, extubation, discharge, or death, whichever comes first). Analysis will occur on an intention-to-treat basis. We aim to enrol 60 patients in total. Recruitment started in January 2024 and is planned to continue for 6 months. Ethics and dissemination: This study received ethical approval (BASEC 2022-00829). Study results will be disseminated through publication in a peer-reviewed journal and other media like podcasts. Trial registration number: NCT058431 ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial NCT05843123 ### Funding Statement Rebeca Mozun and this study is funded by the Children's Research Center of the University Children's Hospital Zurich (FZK Nachwuchsfoerderung grant). Luregn Schlapbach is supported by the grant NDS-2021-911 (SwissPedHealth) from the Swiss Personalized Health Network (SPHN) and the Strategic Focal Area Personalized Health and Related Technologies (PHRT) of the ETH Domain (Swiss Federal Institutes of Technology), by the NOMIS foundation, the Medical Research Future Fund (MRFF), the National Institutes of Health (NIH), the Foundation Sana, the Stiftung fuer naturwissenschaftliche Forschung. Kristen Gibbons is funded by an NHMRC Investigator Grant. Daphne Chopard is funded thorough the grant 2021-911 from the of the Strategic Focal Area Personalized Health and Related Technologies (PHRT) of the ETH Domain (Swiss Federal Institutes of Technology). The funding sources have no involvement in study design, analysis or interpretation of results. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study has received ethical approval (ethics committee of the canton of Zurich, BASEC 2022-00829). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The research team will have access to the dataset of this study. Anonymized data could be available upon reasonable request after approval from the research committee and sponsoring institution.

Roni D. Lane, MD; Troy Richardson, PhD; Halden F. Scott, MD, MSCS; Raina M. Paul, MD; Fran Balamuth, MD, PhD; Matthew A. Eisenberg, MD, MPH; Ruth Riggs; W. Charles Huskins, MD, MSc; Christopher M. Horvat, MD, MHA; Grant E. Keeney, MD, MS; Leslie A. Hueschen, MD; Justin M. Lockwood, MD, MSCS; Vishal Gunnala, MD; Bryan P. McKee, MD; Nikhil Patankar, MD, MBA; Venessa Lynn Pinto, MBBS; Amanda M. Sebring, MD; Matthew P. Sharron, MD; Jennifer Treseler, MSN, RN, CPN, CPHQ; Jennifer J. Wilkes, MD, MSCE; Jennifer K. Workman, MD, MS

BACKGROUND:The neutrophil-to-lymphocyte-ratio (NLR), neutrophil-to-monocyte-plus-lymphocyte-ratio (NMLR) and monocyte-to-lymphocyte-ratio (MLR) may have diagnostic potential for tuberculosis (TB).METHODS:Data of two prospective multicenter studies in Switzerland were used, which included children <18 years with TB exposure, infection or disease or with febrile non-TB lower-respiratory-tract infection (nTB-LRTI).RESULTS:Of the 389 children included 25 (6.4%) had TB disease, 12 (3.1%) TB infection, 28 (7.2%) were healthy TB exposed and 324 (83.3%) nTB-LRTI. Median (IQR) NLR was highest with 2.0 (1.2, 2.2) in children with TB disease compared to TB exposed [0.8 (0.6, 1.3); P = 0.002] and nTB-LRTI [0.3 (0.1, 1.0); P < 0.001]. Median (IQR) NMLR was highest with 1.4 (1.2, 1.7) in children with TB disease compared to healthy exposed [0.7 (0.6, 1.1); P = 0.003] and children with nTB-LRTI [0.2 (0.1, 0.6); P < 0.001). Receiver operating characteristic curves to detect TB disease compared to nTB-LRTI for NLR and NMLR had an area under the curve of 0.82 and 0.86, the sensitivity of 88% and 88%, and specificity of 71% and 76%, respectively.CONCLUSION:NLR and NMLR are promising, easy-to-obtain diagnostic biomarkers to differentiate children with TB disease from other lower respiratory tract infections. These results require validation in a larger study and in settings with high and low TB endemicity.

Transcutaneous PCO2 and PO2 measurement systems offer non-invasive blood gas trend monitoring. The aim of this prospective study was to assess bias and precision of a transcutaneous PCO2 and PO2 measurement system incorporating a novel pO2 sensor (Sentec OxiVenT™) in neonates ≥34 weeks of gestational age (GA) admitted to intensive care.Transcutaneous PCO2 and PO2 were compared to arterial and capillary blood gas measurements. Bias and precision were calculated by fitting linear mixed models to account for repeated measurements, and influence of clinical covariates on bias and precision was assessed.We obtained 611 paired transcutaneous and blood gas measurements in 110 patients (median GA 38.3 [interquartile range 36.1-39.7] weeks; age 9 [4-15] days; weight 3,000 [2,500-3,500] g). Transcutaneous PCO2 showed significant bias to arterial PCO2 (+0.61; 95% confidence interval 0.46, 0.76 kPa), but not to capillary PCO2 (-0.23; -0.46, 0.002 kPa). Bias of transcutaneous PO2 was significant to arterial PO2 (-2.50; -2.94, -2.06 kPa), while no significant bias compared to capillary PO2 was observed (+0.17; -0.30, 0.64 kPa). Precision intervals were ±1.8/2.0 kPa for arterial versus capillary PCO2 and ±4.9/3.3 kPa for arterial versus capillary PO2 comparisons, respectively. Further, sensor operating temperature (43°C vs. 42°C), soft tissue oedema, vasoactive drugs, weight, and GA significantly altered bias (p < 0.05).The tested transcutaneous blood gas measurement system showed no significant bias compared to capillary PCO2 and PO2, acceptable bias to arterial PCO2, and limited agreement with arterial PO2. Precision intervals were wide for all comparisons.

BACKGROUND:Intensive care practice calls for ventilator adjustments due to fast-changing clinical conditions in ventilated critically ill children. These adaptations include positive end-expiratory pressure (PEEP), fraction of inspired oxygen (FiO2), and respiratory rate (RR). It is unclear which alterations in ventilator settings trigger a significant systemic inflammatory response.METHODS:Fourteen-day old Wistar rat pups were randomized to the following groups: (a) "control" with tidal volume ~8 mL/kg, PEEP 5 cmH2O, FiO2 0.4, RR 90 min-1, (b) "PEEP 1", (c) "PEEP 9" (d) "FiO2 0.21", (e) "FiO2 1.0", (f) "hypocapnia" with RR of 180 min-1, and (g) "hypercapnia" with RR of 60 min-1. Following 120 min of mechanical ventilation, plasma for inflammatory biomarker analyses was obtained by direct cardiac puncture at the end of the experiment.RESULTS:Interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were driven by FiO2 0.4 and 1.0 (P=0.02, P<0.01, respectively), tissue plasminogen activator inhibitor type-1 (tPAI-1) was increased by high PEEP (9 cmH2O, P<0.05) and hypocapnia (P<0.05), and TNF-α was significantly lower in hypercapnia (P<0.01). Tissue inhibitor of metalloproteinase-1 (TIMP-1), cytokine-induced neutrophil chemoattractant 1 (CINC-1), connective tissue growth factor (CTGF), and monocyte chemoattractant protein-1 (MCP-1) remained unaffected.CONCLUSION:Alterations of PEEP, FiO2, and respiratory frequency induced a significant systemic inflammatory response in plasma of infant rats. These findings underscore the importance of lung-protective ventilation strategies. However, future studies are needed to clarify whether ventilation induced systemic inflammation in animal models is pathophysiologically relevant to human infants.

Low copeptin levels may indicate inadequate arginine-vasopressin release promoting arterial hypotension, whereas high copeptin concentrations may reflect disease severity. This single-center prospective non-randomized clinical trial analyzed the course of blood copeptin in critically ill normo- and hypotensive children and its association with disease severity. In 164 patients (median age 0.5 years (interquartile range 0.1, 2.9)), the mean copeptin concentration at baseline was 43.5 pmol/L. Though not significantly different after 61 h (primary outcome, mean individual change: −12%, p = 0.36, paired t-test), we detected 1.47-fold higher copeptin concentrations during arterial hypotension when compared to normotension (mixed-effect ANOVA, p = 0.01). In total, 8 out of 34 patients (23.5%) with low copeptin concentrations <10 pmol/L were hypotensive. Copeptin was highest in the adjusted mixed-effect regression analysis within the first day (+20% at 14 h) and decreased significantly at 108 h (−27%) compared to baseline (p = 0.002). Moreover, we found a significant association with vasopressor-inotrope treatment intensity, infancy (1–12 months) and cardiopulmonary bypass (all p ≤ 0.001). In conclusion, high copeptin values were associated with arterial hypotension and severity of disease in critically ill children. This study does not support the hypothesis that low copeptin values might be indicative of arginine-vasopressin deficiency.

Background Cardiovascular impairment contributes to increased mortality in preterm infants with chronic lung disease. Macitentan, an endothelin-1 receptor antagonist, has the potential to attenuate pulmonary and cardiovascular remodelling. Methods In a prospective randomized placebo-controlled intervention trial, Sprague–Dawley rats were exposed to 0.21 or 1.0 fraction of inspired oxygen (FiO 2 ) for 19 postnatal days. Rats were treated via gavage with placebo or macitentan from days of life 5 to 19. Alveoli, pulmonary vessels, α -smooth muscle actin content in pulmonary arterioles, size of cardiomyocytes, right to left ventricular wall diameter ratio, and endothelin-1 plasma concentrations were assessed. Results FiO 2 1.0 induced typical features of chronic lung disease with significant alveolar enlargement (p = 0.012), alveolar (p = 0.048) and pulmonary vessel rarefaction (p = 0.024), higher α -smooth muscle actin content in pulmonary arterioles (p = 0.009), higher right to left ventricular wall diameter ratio (p = 0.02), and larger cardiomyocyte cross-sectional area (p < 0.001). Macitentan treatment significantly increased pulmonary vessel count (p = 0.004) and decreased right to left ventricular wall diameter ratios (p = 0.002). Endothelin-1 plasma concentrations were higher compared to placebo (p = 0.015). Alveolar number and size, α -smooth muscle actin, and the cardiomyocyte cross-sectional area remained unchanged (all p > 0.05). Conclusion The endothelin-1 receptor antagonist macitentan attenuated cardiovascular remodelling in an infant rat model for preterm chronic lung disease. This study underscores the potential of macitentan to reduce cardiovascular morbidity in preterm infants with chronic lung disease.

Background and Objectives: Transcutaneous PCO2 and PO2 measurement systems offer non-invasive blood gas trend monitoring. The aim of this prospective study was to assess bias and precision of a transcutaneous PCO2 and PO2 measurement system incorporating a novel pO2 sensor (Sentec OxiVenT™) in neonates ≥34 weeks of gestational age (GA) admitted to intensive care. Methods: Transcutaneous PCO2 and PO2 were compared to arterial and capillary blood gas measurements. Bias and precision were calculated by fitting linear mixed models to account for repeated measurements, and influence of clinical covariates on bias and precision was assessed. Results: We obtained 611 paired transcutaneous and blood gas measurements in 110 patients (median GA 38.3 [interquartile range 36.1–39.7] weeks; age 9 [4–15] days; weight 3,000 [2,500–3,500] g). Transcutaneous PCO2 showed significant bias to arterial PCO2 (+0.61; 95% confidence interval 0.46, 0.76 kPa), but not to capillary PCO2 (−0.23; −0.46, 0.002 kPa). Bias of transcutaneous PO2 was significant to arterial PO2 (−2.50; −2.94, −2.06 kPa), while no significant bias compared to capillary PO2 was observed (+0.17; −0.30, 0.64 kPa). Precision intervals were ±1.8/2.0 kPa for arterial versus capillary PCO2 and ±4.9/3.3 kPa for arterial versus capillary PO2 comparisons, respectively. Further, sensor operating temperature (43°C vs. 42°C), soft tissue oedema, vasoactive drugs, weight, and GA significantly altered bias (p < 0.05). Conclusions: The tested transcutaneous blood gas measurement system showed no significant bias compared to capillary PCO2 and PO2, acceptable bias to arterial PCO2, and limited agreement with arterial PO2. Precision intervals were wide for all comparisons.

The aminoglycoside gentamicin is used for the empirical treatment of pediatric infections. It has a narrow therapeutic window. In this prospective study at University Children’s Hospital Zurich, Switzerland, we aimed to characterize the pharmacokinetics of gentamicin in pediatric patients and predict plasma concentrations at typical recommended doses. We recruited 109 patients aged from 1 day to 14 years, receiving gentamicin (7.5 mg/kg at age ≥ 7 d or 5 mg/kg). Plasma levels were determined 30 min, 4 h and 24 h after the infusion was stopped and then transferred, together with patient data, to the secure BioMedIT node Leonhard Med. Population pharmacokinetic modeling was performed with the open-source R package saemix on the SwissPKcdw platform in Leonhard Med. Data followed a two-compartment model. Bodyweight, plasma creatinine and urea were identified as covariates for clearance, with bodyweight as a covariate for central and peripheral volumes of distribution. Simulations with 7.5 mg/kg revealed a 95% CI of 13.0–21.2 mg/L plasma concentration at 30 min after the stopping of a 30-min infusion. At 24 h, 95% of simulated plasma levels were <1.8 mg/L. Our study revealed that the recommended dosing is appropriate. It showed that population pharmacokinetic modeling using R provides high flexibility in a secure environment.

Insights from applied respiratory physiology are essential for tailoring mechanical ventilation strategies to a patient's lung function. Despite the potential to improve outcomes clinicians do not routinely take full advantage of available lung function tools. This is unfortunate when considering the burden of prolonged hospital stay on critically ill children and their families. In this review we will a) focus on difficult conditions encountered at bedside when evaluating lung function in critically ill and mechanically ventilated children, b) discuss how improved standardisation can enhance reproducibility and detect disease-specific alterations, c) emphasise the impact of operators when assessing respiratory system mechanics, and d) provide suggestions on how to approach lung function related challenges at bedside.

Rats are often used in ventilator-induced lung injury (VILI) models. However, strain-specific susceptibility for VILI has not been elucidated yet. The aim of this study was to demonstrate strain-specific differences in VILI in infant Sprague-Dawley and Wistar rats. VILI was compared in 2-wk-old pups after 8 h of protective or injurious ventilation. Pups were ventilated with tidal volumes (VT) of ∼7 mL/kg and positive end-expiratory pressures (PEEP) of 6 cmH2O (VT7 PEEP6) or with VT of ∼21 mL/kg and PEEP 2 cmH2O (VT21 PEEP2). Interleukin-6, macrophage inflammatory protein-2 (MIP-2), inflammatory cells, and albumin in bronchoalveolar lavage fluid (BALF); histology; and low-frequency forced oscillation technique (LFOT) and pressure-volume (PV) maneuvers were assessed. Alveolar macrophages, neutrophils, and MIP-2 derived from BALF revealed more pronounced VILI after VT21 PEEP2 in both strains. LFOT and PV analyses demonstrated rat strain-specific differences both at baseline and particularly in response to VT21 PEEP2 ventilation. Sprague-Dawley rats showed higher airway and tissue resistance and elastance values with no difference in hysteresivity between ventilation strategies. Wister rats challenged by VT21 PEEP2 experienced significantly more energy dissipation when compared with VT7 PEEP6 ventilation. In conclusion, both rat strains are useful for VILI models. The degree of VILI severity depends on ventilation strategy and selected strain. However, fundamental and time-dependent differences in respiratory system mechanics exist and reflect different lung tissue viscoelasticity. Hence, strain-specific characteristics of the respiratory system need to be considered when planning and interpreting VILI studies with infant rats.

The poorly understood tolerance toward high tidal volume (V-T) ventilation observed in critically ill children and age-equivalent animal models may be explained by surfactant homeostasis. The aim of our prospective animal study was to test whether high V-T with adequate positive end-expiratory pressure (PEEP) is associated with surfactant de novo synthesis and secretion, leading to improved lung function, and whether extreme mechanical ventilation affects intracellular lamellar body formation and exocytosis. Rats (14 days old) were allocated to five groups: nonventilated controls, PEEP 5 cm H2O with V-T of 8, 16, and 24 mL/kg, and PEEP 1 cmH(2)O with V-T 24 mL/kg. Following 6 h of ventilation, lung function, surfactant proteins and phospholipids, and lamellar bodies were assessed by forced oscillation technique, quantitative real-time polymerase chain reaction, mass spectrometry, immunohistochemistry, and transmission electron microscopy. High V-T (24 mL/kg) with PEEP of 5 cm H2O improved respiratory system mechanics and was not associated with lung injury, elevated surfactant protein expression, or surfactant phospholipid content. Extreme ventilation with V-T 24 mL/kg and PEEP 1 cm H2O produced a mild inflammatory response and correlated with higher surfactant phospholipid concentrations in bronchoalveolar lavage fluid without affecting lamellar body count and morphology. Elevated phospholipid concentrations in the potentially most injurious strategy (V-T 24 mL/kg, PEEP 1 cm H2O) need further evaluation and might reflect accumulation of biophysically inactive small aggregates. In conclusion, our data confirm the resilience of infant rats toward high V-T-induced lung injury and challenge the relevance of surfactant synthesis, storage, and secretion as protective factors.

Hyperoxia-induced bronchopulmonary dysplasia (BPD) models are essential for better understanding and impacting on long-term pulmonary, cardiovascular, and neurological sequelae of this chronic disease. Only few experimental studies have systematically compared structural alterations with lung function measurements.

Mechanical ventilation (MV) is routinely used in pediatric general anesthesia and critical care, but may adversely affect the cardiocirculatory system. Biomarkers are increasingly measured to assess cardiovascular status and improve clinical treatment decision-making. As the impact of mechanical ventilation strategies on cardiovascular biomarkers in ventilated infants is largely unknown, we conducted this retrospective study in a healthy in vivo infant rat ventilation model using 14-days old Wistar rats. We hypothesized that 2 h of mechanical ventilation with high and low positive end-expiratory pressure (PEEP), hyperoxemia, hypoxemia, hypercapnia, and hypocapnia would significantly impact B-type natriuretic peptide (BNP), vascular endothelial growth factor (VEGF), and endothelin-1 (ET-1). We found BNP to be driven by both high (9 cmH(2)O) and low (1 cmH(2)O) PEEP compared to ventilated control animals (P < 0.05). VEGF concentrations were associated with high PEEP, hyperoxemia, hypoxemia, and hypocapnia (P < 0.05), whereas ET-1 levels were changed only in response to hypoxemia (P < 0.05). In conclusion, the mode of mechanical ventilation alters plasma biomarker concentrations. Moreover, BNP and VEGF might serve as surrogate parameters for ventilation induced cardiovascular compromise and lung tissue damage. Furthermore, our data support the hypothesis, that sudden onset of hyperoxemia may trigger a quick VEGF release as a possible cellular survival reflex.

Mortality and morbidity remain high in pediatric lower respiratory tract infections (LRTIs) despite progress in research and implementation of global diagnostic and treatment strategies in the last decade. Still, 120 million annual episodes of pneumonia affect children younger than 5 years each year leading to 1.3 million fatalities with the major burden of disease carried by low- and middle-income countries (95%). The definition of pneumonia is still challenging. Traditional diagnostic measures (i.e., chest radiographs, C-reactive protein) are unable to distinguish viral and from bacterial etiology. As a result, common antibiotic overuse contributes to growing antibiotic resistance. We present an overview of current evidence from observational and randomized controlled trials on a procalcitonin (PCT)-based diagnosis of pediatric LRTIs and discuss the need for an adequate PCT threshold for antibiotic treatment decision-making.