Mechanical and morphological characterization of the emphysematous lung tissue.

Irreversible alveolar airspace enlargement is the main characteristic of pulmonary emphysema, which has been extensively studied using animal models. While the alterations in lung mechanics associated with these morphological changes have been documented in the literature, the study of the mechanical behavior of parenchymal tissue from emphysematous lungs has been poorly investigated. In this work, we characterize the mechanical and morphological properties of lung tissue in elastase-induced emphysema rat models under varying severity conditions. We analyze the non-linear tissue behavior using suitable hyperelastic constitutive models that enable to compare different non-linear responses in terms of hyperelastic material parameters. We further analyze the effect of the elastase dose on alveolar morphology and tissue material parameters and study their connection with respiratory-system mechanical parameters. Our results show that while the lung mechanical function is not significantly influenced by the elastase treatment, the tissue mechanical behavior and alveolar morphology are markedly affected by it. We further show a strong association between alveolar enlargement and tissue softening, not evidenced by respiratory-system compliance. Our findings highlight the importance of understanding tissue mechanics in emphysematous lungs, as changes in tissue properties could detect the early stages of emphysema remodeling. STATEMENT OF SIGNIFICANCE: Gas exchange is vital for life and strongly relies on the mechanical function of the lungs. Pulmonary emphysema is a prevalent respiratory disease where alveolar walls are damaged, causing alveolar enlargement that induces harmful changes in the mechanical response of the lungs. In this work, we study how the mechanical properties of lung tissue change during emphysema. Our results from animal models show that tissue properties are more sensitive to alveolar enlargement due to emphysema than other mechanical properties that describe the function of the whole respiratory system.

Effect of positive end-expiratory pressure on lung injury and haemodynamics during experimental acute respiratory distress syndrome treated with extracorporeal membrane oxygenation and near-apnoeic ventilation.

BACKGROUND: Lung rest has been recommended during extracorporeal membrane oxygenation (ECMO) for severe acute respiratory distress syndrome (ARDS). Whether positive end-expiratory pressure (PEEP) confers lung protection during ECMO for severe ARDS is unclear. We compared the effects of three different PEEP levels whilst applying near-apnoeic ventilation in a model of severe ARDS treated with ECMO. METHODS: Acute respiratory distress syndrome was induced in anaesthetised adult male pigs by repeated saline lavage and injurious ventilation for 1.5 h. After ECMO was commenced, the pigs received standardised near-apnoeic ventilation for 24 h to maintain similar driving pressures and were randomly assigned to PEEP of 0, 10, or 20 cm H2O (n=7 per group). Respiratory and haemodynamic data were collected throughout the study. Histological injury was assessed by a pathologist masked to PEEP allocation. Lung oedema was estimated by wet-to-dry-weight ratio. RESULTS: All pigs developed severe ARDS. Oxygenation on ECMO improved with PEEP of 10 or 20 cm H2O, but did not in pigs allocated to PEEP of 0 cm H2O. Haemodynamic collapse refractory to norepinephrine (n=4) and early death (n=3) occurred after PEEP 20 cm H2O. The severity of lung injury was lowest after PEEP of 10 cm H2O in both dependent and non-dependent lung regions, compared with PEEP of 0 or 20 cm H2O. A higher wet-to-dry-weight ratio, indicating worse lung injury, was observed with PEEP of 0 cm H2O. Histological assessment suggested that lung injury was minimised with PEEP of 10 cm H2O. CONCLUSIONS: During near-apnoeic ventilation and ECMO in experimental severe ARDS, 10 cm H2O PEEP minimised lung injury and improved gas exchange without compromising haemodynamic stability.

Progression of regional lung strain and heterogeneity in lung injury: assessing the evolution under spontaneous breathing and mechanical ventilation.

BACKGROUND: Protective mechanical ventilation (MV) aims at limiting global lung deformation and has been associated with better clinical outcomes in acute respiratory distress syndrome (ARDS) patients. In ARDS lungs without MV support, the mechanisms and evolution of lung tissue deformation remain understudied. In this work, we quantify the progression and heterogeneity of regional strain in injured lungs under spontaneous breathing and under MV. METHODS: Lung injury was induced by lung lavage in murine subjects, followed by 3 h of spontaneous breathing (SB-group) or 3 h of low Vt mechanical ventilation (MV-group). Micro-CT images were acquired in all subjects at the beginning and at the end of the ventilation stage following induction of lung injury. Regional strain, strain progression and strain heterogeneity were computed from image-based biomechanical analysis. Three-dimensional regional strain maps were constructed, from which a region-of-interest (ROI) analysis was performed for the regional strain, the strain progression, and the strain heterogeneity. RESULTS: After 3 h of ventilation, regional strain levels were significantly higher in 43.7% of the ROIs in the SB-group. Significant increase in regional strain was found in 1.2% of the ROIs in the MV-group. Progression of regional strain was found in 100% of the ROIs in the SB-group, whereas the MV-group displayed strain progression in 1.2% of the ROIs. Progression in regional strain heterogeneity was found in 23.4% of the ROIs in the SB-group, while the MV-group resulted in 4.7% of the ROIs showing significant changes. Deformation progression is concurrent with an increase of non-aerated compartment in SB-group (from 13.3% ± 1.6% to 37.5% ± 3.1%), being higher in ventral regions of the lung. CONCLUSIONS: Spontaneous breathing in lung injury promotes regional strain and strain heterogeneity progression. In contrast, low Vt MV prevents regional strain and heterogeneity progression in injured lungs.

A physiological approach to understand the role of respiratory effort in the progression of lung injury in SARS-CoV-2 infection.

Deterioration of lung function during the first week of COVID-19 has been observed when patients remain with insufficient respiratory support. Patient self-inflicted lung injury (P-SILI) is theorized as the responsible, but there is not robust experimental and clinical data to support it. Given the limited understanding of P-SILI, we describe the physiological basis of P-SILI and we show experimental data to comprehend the role of regional strain and heterogeneity in lung injury due to increased work of breathing.In addition, we discuss the current approach to respiratory support for COVID-19 under this point of view.

Mapping regional strain in anesthetised healthy subjects during spontaneous ventilation.

Introduction: Breathing produces a phenomenon of cyclic deformation throughout life. Biomechanically, deformation of the lung is measured as strain. Regional strain recently started to be recognised as a tool in the study of lung pathophysiology, but regional lung strain has not been studied in healthy subjects breathing spontaneously without voluntary or pharmacological control of ventilation. Our aim is to generate three-dimensional (3D) regional strain and heterogeneity maps of healthy rat lungs and describe their changes over time. Methods: Micro-CT and image-based biomechanical analysis by finite element approach were carried out in six anaesthetised rats under spontaneous breathing in two different states, at the beginning of the experiment and after 3 hours of observation. 3D regional strain maps were constructed and divided into 10 isovolumetric region-of-interest (ROI) in three directions (apex to base, dorsal to ventral and costal to mediastinal), allowing to regionally analyse the volumetric strain, the strain progression and the strain heterogeneity. To describe in depth these parameters, and systematise their report, we defined regional strain heterogeneity index [1+strain SD ROI(x)]/[1+strain mean ROI(x)] and regional strain progression index [ROI(x)-mean of final strain/ROI(x)-mean of initial strain]. Results: We were able to generate 3D regional strain maps of the lung in subjects without respiratory support, showing significant differences among the three analysed axes. We observed a significantly lower regional volumetric strain in the apex sector compared with the base, with no significant anatomical systematic differences in the other directions. This heterogeneity could not be identified with physiological or standard CT methods. There was no progression of the analysed regional volumetric strain when the two time-points were compared. Discussion: It is possible to map the regional volumetric strain in the lung for healthy subjects during spontaneous breathing. Regional strain heterogeneity and changes over time can be measured using a CT image-based numerical analysis applying a finite element approach. These results support that healthy lung might have significant regional strain and its spatial distribution is highly heterogeneous. This protocol for CT image acquisition and analysis could be a useful tool for helping to understand the mechanobiology of the lung in many diseases.

Near-Apneic Ventilation Decreases Lung Injury and Fibroproliferation in an Acute Respiratory Distress Syndrome Model with Extracorporeal Membrane Oxygenation.

RATIONALE: There is wide variability in mechanical ventilation settings during extracorporeal membrane oxygenation (ECMO) in patients with acute respiratory distress syndrome. Although lung rest is recommended to prevent further injury, there is no evidence to support it. OBJECTIVES: To determine whether near-apneic ventilation decreases lung injury in a pig model of acute respiratory distress syndrome supported with ECMO. METHODS: Pigs (26-36 kg; n = 24) were anesthetized and connected to mechanical ventilation. In 18 animals lung injury was induced by a double-hit consisting of repeated saline lavages followed by 2 hours of injurious ventilation. Then, animals were connected to high-flow venovenous ECMO, and randomized into three groups: 1) nonprotective (positive end-expiratory pressure [PEEP], 5 cm H2O; Vt, 10 ml/kg; respiratory rate, 20 bpm), 2) conventional-protective (PEEP, 10 cm H2O; Vt, 6 ml/kg; respiratory rate, 20 bpm), and 3) near-apneic (PEEP, 10 cm H2O; driving pressure, 10 cm H2O; respiratory rate, 5 bpm). Six other pigs were used as sham. All groups were maintained during the 24-hour study period. MEASUREMENTS AND MAIN RESULTS: Minute ventilation and mechanical power were lower in the near-apneic group, but no differences were observed in oxygenation or compliance. Lung histology revealed less injury in the near-apneic group. Extensive immunohistochemical staining for myofibroblasts and procollagen III was observed in the nonprotective group, with the near-apneic group exhibiting the least alterations. Near-apneic group showed significantly less matrix metalloproteinase-2 and -9 activity. Histologic lung injury and fibroproliferation scores were positively correlated with driving pressure and mechanical power. CONCLUSIONS: In an acute respiratory distress syndrome model supported with ECMO, near-apneic ventilation decreased histologic lung injury and matrix metalloproteinase activity, and prevented the expression of myofibroblast markers.

Positive end-expiratory pressure improves elastic working pressure in anesthetized children.

BACKGROUND: Positive end-expiratory pressure (PEEP) has been demonstrated to decrease ventilator-induced lung injury in patients under mechanical ventilation (MV) for acute respiratory failure. Recently, some studies have proposed some beneficial effects of PEEP in ventilated patients without lung injury. The influence of PEEP on respiratory mechanics in children is not well known. Our aim was to determine the effects on respiratory mechanics of setting PEEP at 5 cmH2O in anesthetized healthy children. METHODS: Patients younger than 15 years old without history of lung injury scheduled for elective surgery gave informed consent and were enrolled in the study. After usual care for general anesthesia, patients were placed on volume controlled MV. Two sets of respiratory mechanics studies were performed using inspiratory and expiratory breath hold, with PEEP 0 and 5 cmH2O. The maximum inspiratory and expiratory flow (QI and QE) as well as peak inspiratory pressure (PIP), plateau pressure (PPL) and total PEEP (tPEEP) were measured. Respiratory system compliance (CRS), inspiratory and expiratory resistances (RawI and RawE) and time constants (KTI and KTE) were calculated. Data were expressed as median and interquartile range (IQR). Wilcoxon sign test and Spearman's analysis were used. Significance was set at P < 0.05. RESULTS: We included 30 patients, median age 39 (15-61.3) months old, 60% male. When PEEP increased, PIP increased from 12 (11,14) to 15.5 (14,18), and CRS increased from 0.9 (0.9,1.2) to 1.2 (0.9,1.4) mL·kg- 1·cmH2O- 1; additionally, when PEEP increased, driving pressure decreased from 6.8 (5.9,8.1) to 5.8 (4.7,7.1) cmH2O, and QE decreased from 13.8 (11.8,18.7) to 11.7 (9.1,13.5) L·min- 1 (all P < 0.01). There were no significant changes in resistance and QI. CONCLUSIONS: Analysis of respiratory mechanics in anesthetized healthy children shows that PEEP at 5 cmH2O places the respiratory system in a better position in the P/V curve. A better understanding of lung mechanics may lead to changes in the traditional ventilatory approach, limiting injury associated with MV.

Implementation of preemptive fluid strategy as a bundle to prevent fluid overload in children with acute respiratory distress syndrome and sepsis.

BACKGROUND: Fluid overload (FO) is associated with unfavorable outcomes in critically ill children. Clinicians are encouraged to avoid FO; however, strategies to avoid FO are not well-described in pediatrics. Our aim was to implement a bundle strategy to prevent FO in children with sepsis and pARDS and to compare the outcomes with a historical cohort. METHODS: A quality improvement initiative, known as preemptive fluid strategy (PFS) was implemented to prevent early FO, in a 12-bed general PICU. Infants on mechanical ventilation (MV) fulfilling pARDS and sepsis criteria were prospectively recruited. For comparison, data from a historical cohort from 2015, with the same inclusion and exclusion criteria, was retrospectively reviewed. The PFS bundle consisted of 1. maintenance of intravenous fluids (MIVF) at 50% of requirements; 2. drug volume reduction; 3. dynamic monitoring of preload markers to determine the need for fluid bolus administration; 4. early use of diuretics; and 5. early initiation of enteral feeds. The historical cohort treatment, the standard fluid strategy (SFS), were based on physician preferences. Peak fluid overload (PFO) was the primary outcome. PFO was defined as the highest FO during the first 72 h. FO was calculated as (cumulative fluid input - cumulative output)/kg*100. Fluid input/output were registered every 12 h for 72 h. RESULTS: Thirty-seven patients were included in the PFS group (54% male, 6 mo (IQR 2,11)) and 39 with SFS (64%male, 3 mo (IQR1,7)). PFO was lower in PFS (6.31% [IQR4.4-10]) compared to SFS (12% [IQR8.4-15.8]). FO was lower in PFS compared to CFS as early as 12 h after admission [2.4(1.4,3.7) v/s 4.3(1.5,5.5), p < 0.01] and maintained during the study. These differences were due to less fluid input (MIVF and fluid boluses). There were no differences in the renal function test. PRBC requirements were lower during the first 24 h in the PFS (5%) compared to SFS (28%, p < 0.05). MV duration was 81 h (58,98) in PFS and 118 h (85154) in SFS(p < 0.05). PICU LOS in PFS was 5 (4, 7) and in SFS was 8 (6, 10) days. CONCLUSION: Implementation of a bundle to prevent FO in children on MV with pARDS and sepsis resulted in less PFO. We observed a decrease in MV duration and PICU LOS. Future studies are needed to address if PFS might have a positive impact on health outcomes.

Extracorporeal membrane oxygenation improves survival in a novel 24-hour pig model of severe acute respiratory distress syndrome.

Extracorporeal membrane oxygenation (ECMO) is increasingly being used to treat severe acute respiratory distress syndrome (ARDS). However, there is limited clinical evidence about how to optimize the technique. Experimental research can provide an alternative to fill the actual knowledge gap. The purpose of the present study was to develop and validate an animal model of acute lung injury (ALI) which resembled severe ARDS, and which could be successfully supported with ECMO. Eighteen pigs were randomly allocated into three groups: sham, ALI, and ALI + ECMO. ALI was induced by a double-hit consisting in repeated saline lavage followed by a 2-hour period of injurious ventilation. All animals were followed up to 24 hours while being ventilated with conventional ventilation (tidal volume 10 ml/kg). The lung injury model resulted in severe hypoxemia, increased airway pressures, pulmonary hypertension, and altered alveolar membrane barrier function, as indicated by an increased protein concentration in bronchoalveolar fluid, and increased wet/dry lung weight ratio. Histologic examination revealed severe diffuse alveolar damage, characteristic of ARDS. Veno-venous ECMO was started at the end of lung injury induction with a flow > 60 ml/kg/min resulting in rapid reversal of hypoxemia and pulmonary hypertension. Mortality was 0, 66.6 and 16.6% in the SHAM, ALI and ALI + ECMO groups, respectively (p < 0.05). This is a novel clinically relevant animal model that can be used to optimize the approach to ECMO and foster translational research in extracorporeal lung support.

Regenerative Potential of Mesenchymal Stromal Cells: Age-Related Changes.

Preclinical and clinical studies have shown that a therapeutic effect results from mesenchymal stromal cells (MSCs) transplant. No systematic information is currently available regarding whether donor age modifies MSC regenerative potential on cutaneous wound healing. Here, we evaluate whether donor age influences this potential. Two different doses of bone marrow MSCs (BM-MSCs) from young, adult, or old mouse donors or two doses of their acellular derivatives mesenchymal stromal cells (acd-MSCs) were intradermally injected around wounds in the midline of C57BL/6 mice. Every two days, wound healing was macroscopically assessed (wound closure) and microscopically assessed (reepithelialization, dermal-epidermal junction, skin appendage regeneration, granulation tissue, leukocyte infiltration, and density dermal collagen fibers) after 12 days from MSC transplant. Significant differences in the wound closure kinetic, quality, and healing of skin regenerated were observed in lesions which received BM-MSCs from different ages or their acd-MSCs compared to lesions which received vehicle. Nevertheless, our data shows that adult's BM-MSCs or their acd-MSCs were the most efficient for recovery of most parameters analyzed. Our data suggest that MSC efficacy was negatively affected by donor age, where the treatment with adult's BM-MSCs or their acd-MSCs in cutaneous wound promotes a better tissue repair/regeneration. This is due to their paracrine factors secretion.

Decreased lung compliance increases preload dynamic tests in a pediatric acute lung injury model / Una compliance pulmonar disminuida incrementa los test dinámicos de precarga en un modelo pediátrico de lesión pulmonar aguda

Background: Preload dynamic tests, pulse pressure variation (PPV) and stroke volume variation (SVV) have emerged as powerful tools to predict response to fluid administration. The influence of factors other than preload in dynamic preload test is currently poorly understood in pediatrics. The aim of our study was to assess the effect of tidal volume (V T) on PPV and SVV in the context of normal and reduced lung compliance in a piglet model. Material and method: Twenty large-white piglets (5.2 ± 0.4 kg) were anesthetized, paralyzed and monitored with pulse contour analysis. PPV and SVV were recorded during mechanical ventilation with a V T of 6 and 12 mL/kg (low and high V T, respectively), both before and after tracheal instillation of polysorbate 20. Results: Before acute lung injury (ALI) induction, modifications of V T did not significantly change PPV and SVV readings. After ALI, PPV and SVV were significantly greater during ventilation with a high V T compared to a low V T (PPV increased from 8.9 ± 1.2 to 12.4 ± 1.1%, and SVV from 8.5 ± 1.0 to 12.7 ± 1.2%, both P < 0.01). Conclusions: This study found that a high V T and reduced lung compliance due to ALI increase preload dynamic tests, with a greater influence of the latter. In subjects with ALI, lung compliance should be considered when interpreting the preload dynamic tests.

Introducción: Test dinámicos de precarga, variación de presión de pulso (PPV) y variación de volumen sistólico (SVV) han emergido como herramientas poderosas para predecir respuesta a la administración de fluidos. Actualmente la influencia de factores distintos a la precarga en la determinación de los test dinámicos de precarga es pobremente conocida en pediatría. Nuestro objetivo fue medir el efecto del volumen tidal (V T) sobre PPV y SVV en un contexto de compliance pulmonar normal y disminuida en un modelo porcino. Material y método: Veinte cerditos Large-White anestesiados y paralizados (5,2 ± 0,4 kg). PPV y SVV fueron medidos por análisis de contorno de pulso durante ventilación con V T de 6 y 12 mL/kg (V T bajo y alto, respectivamente), ambos previo y posterior a lesión pulmonar aguda (ALI) químicamente inducida con instilación traqueal de polisorbato 20. Resultados: Previo a inducción de ALI, PPV y SVV no tuvieron cambios significativos al modificar el V T. Sin embargo, después de ALI, PPV y SVV fueron significativamente mayores durante ventilación con V T alto, respecto a V T bajo (PPV aumentó de 8,9 ± 1,2 a 12,4 ± 1,1%, y SVV de 8,5 ± 1,0 a 12,7 ± 1,2%, ambos P < 0,01). Conclusiones: Este estudio encontró que un V T alto y una compliance pulmonar disminuida debido a ALI incrementan los test dinámicos de precarga, con una mayor influencia de esta última. En sujetos con ALI la compliance pulmonar debiera ser considerada al interpretar los test dinámicos de precarga.

Decreased lung compliance increases preload dynamic tests in a pediatric acute lung injury model.

BACKGROUND: Preload dynamic tests, pulse pressure variation (PPV) and stroke volume variation (SVV) have emerged as powerful tools to predict response to fluid administration. The influence of factors other than preload in dynamic preload test is currently poorly understood in pediatrics. The aim of our study was to assess the effect of tidal volume (VT) on PPV and SVV in the context of normal and reduced lung compliance in a piglet model. MATERIAL AND METHOD: Twenty large-white piglets (5.2±0.4kg) were anesthetized, paralyzed and monitored with pulse contour analysis. PPV and SVV were recorded during mechanical ventilation with a VT of 6 and 12mL/kg (low and high VT, respectively), both before and after tracheal instillation of polysorbate 20. RESULTS: Before acute lung injury (ALI) induction, modifications of VT did not significantly change PPV and SVV readings. After ALI, PPV and SVV were significantly greater during ventilation with a high VT compared to a low VT (PPV increased from 8.9±1.2 to 12.4±1.1%, and SVV from 8.5±1.0 to 12.7±1.2%, both P<0.01). CONCLUSIONS: This study found that a high VT and reduced lung compliance due to ALI increase preload dynamic tests, with a greater influence of the latter. In subjects with ALI, lung compliance should be considered when interpreting the preload dynamic tests.

Mild hypothermia increases pulmonary anti-inflammatory response during protective mechanical ventilation in a piglet model of acute lung injury.

BACKGROUND: The effects of mild hypothermia (HT) on acute lung injury (ALI) are unknown in species with metabolic rate similar to that of humans, receiving protective mechanical ventilation (MV). We hypothesized that mild hypothermia would attenuate pulmonary and systemic inflammatory responses in piglets with ALI managed with a protective MV. METHODS: Acute lung injury (ALI) was induced with surfactant deactivation in 38 piglets. The animals were then ventilated with low tidal volume, moderate positive end-expiratory pressure (PEEP), and permissive hypercapnia throughout the experiment. Subjects were randomized to HT (33.5°C) or normothermia (37°C) groups over 4 h. Plasma and tissue cytokines, tissue apoptosis, lung mechanics, pulmonary vascular permeability, hemodynamic, and coagulation were evaluated. RESULTS: Lung interleukin-10 concentrations were higher in subjects that underwent HT after ALI induction than in those that maintained normothermia. No difference was found in other systemic and tissue cytokines. HT did not induce lung or kidney tissue apoptosis or influence lung mechanics or markers of pulmonary vascular permeability. Heart rate, cardiac output, oxygen uptake, and delivery were significantly lower in subjects that underwent HT, but no difference in arterial lactate, central venous oxygen saturation, and coagulation test was observed. CONCLUSIONS: Mild hypothermia induced a local anti-inflammatory response in the lungs, without affecting lung function or coagulation, in this piglet model of ALI. The HT group had lower cardiac output without signs of global dysoxia, suggesting an adaptation to the decrease in oxygen uptake and delivery. Studies are needed to determine the therapeutic role of HT in ALI.

Surfactant deactivation in a pediatric model induces hypovolemia and fluid shift to the extravascular lung compartment.

BACKGROUND: Surfactant deficiency is the pivotal abnormality in Neonatal and Acute Respiratory Distress Syndrome. Surfactant deactivation can produce hypoxemia, loss of lung compliance, and pulmonary edema, but its circulatory consequences are less understood. OBJECTIVE: To describe the sequential hemodynamic changes and pulmonary edema formation after surfactant deactivation in piglets. METHODS: Surfactant deactivation was induced by tracheal instillation of polysorbate 20 in 15 anesthetized and mechanically ventilated Large White piglets. The hemodynamic consequences of surfactant deactivation were assessed at 30, 120, and 240 min by transpulmonary thermodilution and traditional methods. RESULTS: Surfactant deactivation caused hypoxemia, reduced lung compliance, and progressively increased lung water content (P < 0.01). Early hypovolemia was observed, with reductions of the global end-diastolic volume and stroke volume (P < 0.05). Reduced cardiac output was observed at the end of the study (P < 0.05). Standard monitoring was unable to detect these early preload alterations. Surprisingly, the bronchoalveolar protein content was greatly increased at the end of the study compared with baseline levels (P < 0.01). This finding was inconsistent with the notion that the pulmonary edema induced by surfactant deactivation was exclusively caused by high surface tension. CONCLUSIONS: Hypovolemia develops early after surfactant deactivation, in part due to the resulting fluid shift from the intravascular compartment to the lungs.

[Veno-arterial difference of carbon dioxide as a predictor of low cardiac output in an experimental pediatric model]. / Diferencia veno-arterial de dióxido de carbono como predictor de gasto cardiaco disminuido en modelo pediátrico experimental.

BACKGROUND: Cardiac output (CO) measurement is not a standard of care for critically ill children, but it can be estimated by indirect methods such as veno-arterial pCO2 difference (ΔVACO2). AIM: To determine the correlation between CO and ΔVACO2 and evaluate the usefulness of ΔVACO2 in the diagnosis of low CO in an experimental pediatric model. MATERIALS AND METHODS: Thirty piglets weighing 4.8 ± 0.35 kg were anesthetized and monitored with transpulmonary thermodilution. Lung injury was induced with tracheal instillation of Tween 20®. Serial measurements of central venous and arterial blood gases, as well as CO, were obtained at baseline, 1, 2 and 4 h after lung injury induction. Low cardiac output (LCO) was defined as CO lower than 2.5 Llminlm². RESULTS: There was an inverse correlation between CO and ΔVACO2 (r = -0.36, p < 0.01). ΔVACO2 was 14 ± 8 mmHg in LCO state and 8 ± 6 mmHg when this condition was not present (p < 0.01). Area under the receiver operating characteristic (ROC) curves of ΔVACO2 and LCO state was 0.78 (0.68-0.86). The best cut-point was 8.9 mmHg to determine LCO with a sensibility 0.78, specificity 0.7, positive predictive value 0.27 and negative predictive value 0.96. CONCLUSIONS: In this model there was an inverse correlation between ΔVACO2 and CO. The best cutoff value to discard LCO was ΔVACO2 of 8.9 mmHg, indicating that under this value the presence of LCO is very unlikely.

Diferencia veno-arterial de dióxido de carbono como predictor de gasto cardiaco disminuido en modelo pediátrico experimental / Veno-arterial difference of carbondioxide as a predictor of low cardiac output in an experimental pediatric model

Background: Cardiac output (CO) measurement is not a standard of care for critically ill children, but it can be estimated by indirect methods such as veno-arterial pCO2 difference (ΔVACO2). Aim: To determine the correlation between CO and ΔVACO2 and evaluate the usefulness of ΔVACO2 in the diagnosis of low CO in an experimental pediatric model. Materials and Methods: Thirty piglets weighing 4.8 ± 0.35 kg were anesthetized and monitored with transpulmonary thermodilution. Lung injury was induced with tracheal instillation of Tween 20®. Serial measurements of central venous and arterial blood gases, as well as CO, were obtained at baseline, 1, 2 and 4 h after lung injury induction. Low cardiac output (LCO) was defined as CO lower than 2.5 Llminlm². Results: There was an inverse correlation between CO and ΔVACO2 (r = -0.36, p < 0.01). ΔVACO2 was 14 ± 8 mmHg in LCO state and 8 ± 6 mmHg when this condition was not present (p < 0.01). Area under the receiver operating characteristic (ROC) curves of ΔVACO2 and LCO state was 0.78 (0.68-0.86). The best cut-point was 8.9 mmHg to determine LCO with a sensibility 0.78, specificity 0.7, positive predictive value 0.27 and negative predictive value 0.96. Conclusions: In this model there was an inverse correlation between ΔVACO2 and CO. The best cutoff value to discard LCO was ΔVACO2 of 8.9 mmHg, indicating that under this value the presence of LCO is very unlikely.

Angiotensin-converting enzyme insertion/deletion polymorphism is associated with severe hypoxemia in pediatric ARDS.

PURPOSE: The D allele of the insertion/deletion (I/D) polymorphism of a 287-bp sequence in the angiotensin-converting enzyme (ACE) gene has been associated with an increased activity of this enzyme. Its role in susceptibility to acute respiratory distress syndrome (ARDS) has not been well defined. We hypothesized that ACE I/D genotype in pediatrics is associated with ARDS and plasma levels of angiotensin II. METHODS: Prospective case-control study in patients under 15 years of age from a mixed Chilean population. Sixty patients with ARDS and 60 controls were included. Association between ACE genotype and ARDS was evaluated as the primary outcome; mortality and severe hypoxemia were examined as secondary outcomes. Plasma angiotensin-II concentration was measured by immunoassay at admission. RESULTS: Frequency of ACE I/D genotype was similar in ARDS and control groups (p = 0.18). In the ARDS group, severe hypoxemia was less frequent in D allele carriers (p < 0.05). Plasma angiotensin-II levels were associated with genotype in the ARDS group, but not controls, being higher in D allele carriers (p = 0.016). CONCLUSION: These data do not support the association between ACE I/D genotype and ARDS, although severe hypoxemia was less frequent in D allele carriers. ACE I/D polymorphism modified angiotensin-II levels in pediatric ARDS, but its pathogenic role is not well understood and needs to be addressed in future studies.