Effects of prone positioning on lung mechanical power components in patients with acute respiratory distress syndrome: a physiologic study.

BACKGROUND: Prone positioning (PP) homogenizes ventilation distribution and may limit ventilator-induced lung injury (VILI) in patients with moderate to severe acute respiratory distress syndrome (ARDS). The static and dynamic components of ventilation that may cause VILI have been aggregated in mechanical power, considered a unifying driver of VILI. PP may affect mechanical power components differently due to changes in respiratory mechanics; however, the effects of PP on lung mechanical power components are unclear. This study aimed to compare the following parameters during supine positioning (SP) and PP: lung total elastic power and its components (elastic static power and elastic dynamic power) and these variables normalized to end-expiratory lung volume (EELV). METHODS: This prospective physiologic study included 55 patients with moderate to severe ARDS. Lung total elastic power and its static and dynamic components were compared during SP and PP using an esophageal pressure-guided ventilation strategy. In SP, the esophageal pressure-guided ventilation strategy was further compared with an oxygenation-guided ventilation strategy defined as baseline SP. The primary endpoint was the effect of PP on lung total elastic power non-normalized and normalized to EELV. Secondary endpoints were the effects of PP and ventilation strategies on lung elastic static and dynamic power components non-normalized and normalized to EELV, respiratory mechanics, gas exchange, and hemodynamic parameters. RESULTS: Lung total elastic power (median [interquartile range]) was lower during PP compared with SP (6.7 [4.9-10.6] versus 11.0 [6.6-14.8] J/min; P < 0.001) non-normalized and normalized to EELV (3.2 [2.1-5.0] versus 5.3 [3.3-7.5] J/min/L; P < 0.001). Comparing PP with SP, transpulmonary pressures and EELV did not significantly differ despite lower positive end-expiratory pressure and plateau airway pressure, thereby reducing non-normalized and normalized lung elastic static power in PP. PP improved gas exchange, cardiac output, and increased oxygen delivery compared with SP. CONCLUSIONS: In patients with moderate to severe ARDS, PP reduced lung total elastic and elastic static power compared with SP regardless of EELV normalization because comparable transpulmonary pressures and EELV were achieved at lower airway pressures. This resulted in improved gas exchange, hemodynamics, and oxygen delivery. TRIAL REGISTRATION: German Clinical Trials Register (DRKS00017449). Registered June 27, 2019. https://drks.de/search/en/trial/DRKS00017449.

Preload Responsiveness in Patients With Acute Respiratory Distress Syndrome Managed With Extracorporeal Membrane Oxygenation.

A restrictive fluid strategy is recommended in patients with acute respiratory distress syndrome (ARDS) managed with venovenous extracorporeal membrane oxygenation (VV ECMO). However, there are no established predictors for preload responsiveness in these patients. In 20 ARDS patients managed with VV ECMO, transesophageal echocardiography was used to repeatedly evaluate dynamic parameters of the left (velocity and stroke volume variation) and right ventricular outflow tract (velocity [respiratory variations of the maximal Doppler velocity in the truncus pulmonalis {ΔV max TP}] and velocity time integral [respiratory variation of the velocity time integral measured in the truncus pulmonalis {ΔVTI_TP}] variation in the truncus pulmonalis), the diameter variation in the superior and inferior vena cava and stroke volume variation measured by pulse contour analysis (SVV_PCA). Patients were categorized as responders and nonresponders according to an increase in stroke volume measured by echocardiography during a Passive Leg Raise Test with a cutoff value ≥10%. The final analysis includes 86 measurements. Predictive values for preload responsiveness were found for ΔV max TP (area under the curve [AUC] of 0.64), ΔVTI_TP (AUC 0.67), and SVV_PCA (AUC 0.74). In conclusion, SVV_PCA and, to a lesser extent, ΔV max TP and ΔVTI_TP are the most accurate parameters to predict preload responsiveness in ARDS patients managed with VV ECMO. Transesophageal echocardiography offers no advantages over pulse contour analysis for predicting preload responsiveness and provides only intermittent monitoring and assessment.

Effects of different positive end-expiratory pressure titration strategies on mechanical power during ultraprotective ventilation in ARDS patients treated with veno-venous extracorporeal membrane oxygenation: A prospective interventional study.

PURPOSE: Ultraprotective ventilation in acute respiratory distress syndrome (ARDS) patients with veno-venous extracorporeal membrane oxygenation (VV ECMO) reduces mechanical power (MP) through changes in positive end-expiratory pressure (PEEP); however, the optimal approach to titrate PEEP is unknown. This study assesses the effects of three PEEP titration strategies on MP, hemodynamic parameters, and oxygen delivery in twenty ARDS patients with VV ECMO. MATERIAL AND METHODS: PEEP was titrated according to: (A) a PEEP of 10 cmH2O representing the lowest recommendation by the Extracorporeal Life Support Organization (PEEPELSO), (B) the highest static compliance of the respiratory system (PEEPCstat,RS), and (C) a target end-expiratory transpulmonary pressure of 0 cmH2O (PEEPPtpexp). RESULTS: PEEPELSO was lower compared to PEEPCstat,RS and PEEPPtpexp (10.0 ± 0.0 vs. 16.2 ± 4.7 cmH2O and 17.3 ± 4.0 cmH2O, p < 0.001 each, respectively). PEEPELSO reduced MP compared to PEEPCstat,RS and PEEPPtpexp (5.3 ± 1.3 vs. 6.8 ± 2.0 and 6.9 ± 2.3 J/min, p < 0.001 each, respectively). PEEPELSO resulted in less lung stress compared to PEEPCstat,RS (p = 0.011) and PEEPPtpexp (p < 0.001) and increased cardiac output and oxygen delivery (p < 0.001 each). CONCLUSIONS: An empirical PEEP of 10 cmH2O minimized MP, provided favorable hemodynamics, and increased oxygen delivery in ARDS patients treated with VV ECMO. TRIAL REGISTRATION: German Clinical Trials Register (DRKS00013967). Registered 02/09/2018https://drks.de/search/en/trial/DRKS00013967.

Climate change and fluid status in children: early education as one response to an emerging public health problem.

OBJECTIVE: As global warming intensifies, residents of temperate regions will also face heat waves in the near future. Food habits are one component in addressing the global challenge of climate change. However, water, the most important food for humans, has not been adequately addressed. DESIGN: For this commentary, on the one hand, publications on the increasing heat stress of children were consulted. On the other hand, publications on the special demands of children's temperature regulation in hot environments on fluid balance were analysed. SETTING: The situation of young children in care facilities on days with heat stress is presented as a scenario. In this way, the effects of climatic changes on fluid balance can be estimated and measures to reduce heat stress and stabilise the fluid balance of children can be developed. PARTICIPANTS: For this analysis, first, infants will be considered in order to identify their specific fluid needs. Second, the possibilities for caregivers to improve fluid intake and train appropriate drinking habits already in infancy will be highlighted. RESULTS: Climate change should be included in recommendations on hydration for children. The need to adapt drinking habits requires educational approaches to weather and water - starting in early childhood care. CONCLUSIONS: In the face of rapid climate change, countries must act now by protecting, preparing and prioritising the high-risk group of children. Particular focus should be placed on supporting adequate hydration.

Effects of individualised positive end-expiratory pressure titration on respiratory and haemodynamic parameters during the Trendelenburg position with pneumoperitoneum: A randomised crossover physiologic trial.

BACKGROUND: The Trendelenburg position with pneumoperitoneum during surgery promotes dorsobasal atelectasis formation, which impairs respiratory mechanics and increases lung stress and strain. Positive end-expiratory pressure (PEEP) can reduce pulmonary inhomogeneities and preserve end-expiratory lung volume (EELV), resulting in decreased inspiratory strain and improved gas-exchange. The optimal intraoperative PEEP strategy is unclear. OBJECTIVES: To compare the effects of individualised PEEP titration strategies on set PEEP levels and resulting transpulmonary pressures, respiratory mechanics, gas-exchange and haemodynamics during Trendelenburg position with pneumoperitoneum. DESIGN: Prospective, randomised, crossover single-centre physiologic trial. SETTING: University hospital. PATIENTS: Thirty-six patients receiving robot-assisted laparoscopic radical prostatectomy. INTERVENTIONS: Randomised sequence of three different PEEP strategies: standard PEEP level of 5 cmH 2 O (PEEP 5 ), PEEP titration targeting a minimal driving pressure (PEEP ΔP ) and oesophageal pressure-guided PEEP titration (PEEP Poeso ) targeting an end-expiratory transpulmonary pressure ( PTP ) of 0 cmH 2 O. MAIN OUTCOME MEASURES: The primary endpoint was the PEEP level when set according to PEEP ΔP and PEEP Poeso compared with PEEP of 5 cmH 2 O. Secondary endpoints were respiratory mechanics, lung volumes, gas-exchange and haemodynamic parameters. RESULTS: PEEP levels differed between PEEP ΔP , PEEP Poeso and PEEP5 (18.0 [16.0 to 18.0] vs. 20.0 [18.0 to 24.0]vs. 5.0 [5.0 to 5.0] cmH 2 O; P  < 0.001 each). End-expiratory PTP and lung volume were lower in PEEP ΔP compared with PEEP Poeso ( P  = 0.014 and P  < 0.001, respectively), but driving pressure, lung stress, as well as respiratory system and dynamic elastic power were minimised using PEEP ΔP ( P  < 0.001 each). PEEP ΔP and PEEP Poeso improved gas-exchange, but PEEP Poeso resulted in lower cardiac output compared with PEEP 5 and PEEP ΔP . CONCLUSION: PEEP ΔP ameliorated the effects of Trendelenburg position with pneumoperitoneum during surgery on end-expiratory PTP and lung volume, decreased driving pressure and dynamic elastic power, as well as improved gas-exchange while preserving cardiac output. TRIAL REGISTRATION: German Clinical Trials Register (DRKS00028559, date of registration 2022/04/27). https://drks.de/search/en/trial/DRKS00028559.

Individualized Positive End-expiratory Pressure Titration Strategies in Superobese Patients Undergoing Laparoscopic Surgery: Prospective and Nonrandomized Crossover Study.

BACKGROUND: Superobesity and laparoscopic surgery promote negative end-expiratory transpulmonary pressure that causes atelectasis formation and impaired respiratory mechanics. The authors hypothesized that end-expiratory transpulmonary pressure differs between fixed and individualized positive end-expiratory pressure (PEEP) strategies and mediates their effects on respiratory mechanics, end-expiratory lung volume, gas exchange, and hemodynamic parameters in superobese patients. METHODS: In this prospective, nonrandomized crossover study including 40 superobese patients (body mass index 57.3 ± 6.4 kg/m2) undergoing laparoscopic bariatric surgery, PEEP was set according to (1) a fixed level of 8 cm H2O (PEEPEmpirical), (2) the highest respiratory system compliance (PEEPCompliance), or (3) an end-expiratory transpulmonary pressure targeting 0 cm H2O (PEEPTranspul) at different surgical positioning. The primary endpoint was end-expiratory transpulmonary pressure at different surgical positioning; secondary endpoints were respiratory mechanics, end-expiratory lung volume, gas exchange, and hemodynamic parameters. RESULTS: Individualized PEEPCompliance compared to fixed PEEPEmpirical resulted in higher PEEP (supine, 17.2 ± 2.4 vs. 8.0 ± 0.0 cm H2O; supine with pneumoperitoneum, 21.5 ± 2.5 vs. 8.0 ± 0.0 cm H2O; and beach chair with pneumoperitoneum; 15.8 ± 2.5 vs. 8.0 ± 0.0 cm H2O; P < 0.001 each) and less negative end-expiratory transpulmonary pressure (supine, -2.9 ± 2.0 vs. -10.6 ± 2.6 cm H2O; supine with pneumoperitoneum, -2.9 ± 2.0 vs. -14.1 ± 3.7 cm H2O; and beach chair with pneumoperitoneum, -2.8 ± 2.2 vs. -9.2 ± 3.7 cm H2O; P < 0.001 each). Titrated PEEP, end-expiratory transpulmonary pressure, and lung volume were lower with PEEPCompliance compared to PEEPTranspul (P < 0.001 each). Respiratory system and transpulmonary driving pressure and mechanical power normalized to respiratory system compliance were reduced using PEEPCompliance compared to PEEPTranspul. CONCLUSIONS: In superobese patients undergoing laparoscopic surgery, individualized PEEPCompliance may provide a feasible compromise regarding end-expiratory transpulmonary pressures compared to PEEPEmpirical and PEEPTranspul, because PEEPCompliance with slightly negative end-expiratory transpulmonary pressures improved respiratory mechanics, lung volumes, and oxygenation while preserving cardiac output.

Effects of changes in veno-venous extracorporeal membrane oxygenation blood flow on the measurement of intrathoracic blood volume and extravascular lung water index: a prospective interventional study.

In severe acute respiratory distress syndrome (ARDS), veno-venous extracorporeal membrane oxygenation (V-V ECMO) has been proposed as a therapeutic strategy to possibly reduce mortality. Transpulmonary thermodilution (TPTD) enables monitoring of the extravascular lung water index (EVLWI) and cardiac preload parameters such as intrathoracic blood volume index (ITBVI) in patients with ARDS, but it is not generally recommended during V-V ECMO. We hypothesized that the amount of extracorporeal blood flow (ECBF) influences the calculation of EVLWI and ITBVI due to recirculation of indicator, which affects the measurement of the mean transit time (MTt), the time between injection and passing of half the indicator, as well as downslope time (DSt), the exponential washout of the indicator. EVLWI and ITBVI were measured in 20 patients with severe ARDS managed with V-V ECMO at ECBF rates from 6 to 4 and 2 l/min with TPTD. MTt and DSt significantly decreased when ECBF was reduced, resulting in a decreased EVLWI (26.1 [22.8-33.8] ml/kg at 6 l/min ECBF vs 22.4 [15.3-31.6] ml/kg at 4 l/min ECBF, p < 0.001; and 13.2 [11.8-18.8] ml/kg at 2 l/min ECBF, p < 0.001) and increased ITBVI (840 [753-1062] ml/m2 at 6 l/min ECBF vs 886 [658-979] ml/m2 at 4 l/min ECBF, p < 0.001; and 955 [817-1140] ml/m2 at 2 l/min ECBF, p < 0.001). In patients with severe ARDS managed with V-V ECMO, increasing ECBF alters the thermodilution curve, resulting in unreliable measurements of EVLWI and ITBVI. German Clinical Trials Register (DRKS00021050). Registered 14/08/2018. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00021050.

Ultraprotective versus apneic ventilation in acute respiratory distress syndrome patients with extracorporeal membrane oxygenation: a physiological study.

BACKGROUND: Even an ultraprotective ventilation strategy in severe acute respiratory distress syndrome (ARDS) patients treated with extracorporeal membrane oxygenation (ECMO) might induce ventilator-induced lung injury and apneic ventilation with the sole application of positive end-expiratory pressure may, therefore, be an alternative ventilation strategy. We, therefore, compared the effects of ultraprotective ventilation with apneic ventilation on oxygenation, oxygen delivery, respiratory system mechanics, hemodynamics, strain, air distribution and recruitment of the lung parenchyma in ARDS patients with ECMO. METHODS: In a prospective, monocentric physiological study, 24 patients with severe ARDS managed with ECMO were ventilated using ultraprotective ventilation (tidal volume 3 ml/kg of predicted body weight) with a fraction of inspired oxygen (FiO2) of 21%, 50% and 90%. Patients were then treated with apneic ventilation with analogous FiO2. The primary endpoint was the effect of the ventilation strategy on oxygenation and oxygen delivery. The secondary endpoints were mechanical power, stress, regional air distribution, lung recruitment and the resulting strain, evaluated by chest computed tomography, associated with the application of PEEP (apneic ventilation) and/or low VT (ultraprotective ventilation). RESULTS: Protective ventilation, compared to apneic ventilation, improved oxygenation (arterial partial pressure of oxygen, p < 0.001 with FiO2 of 50% and 90%) and reduced cardiac output. Both ventilation strategies preserved oxygen delivery independent of the FiO2. Protective ventilation increased driving pressure, stress, strain, mechanical power, as well as induced additional recruitment in the non-dependent lung compared to apneic ventilation. CONCLUSIONS: In patients with severe ARDS managed with ECMO, ultraprotective ventilation compared to apneic ventilation improved oxygenation, but increased stress, strain, and mechanical power. Apneic ventilation might be considered as one of the options in the initial phase of ECMO treatment in severe ARDS patients to facilitate lung rest and prevent ventilator-induced lung injury. TRIAL REGISTRATION: German Clinical Trials Register (DRKS00013967). Registered 02/09/2018. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00013967 .

Effects of different positive end-expiratory pressure titration strategies during prone positioning in patients with acute respiratory distress syndrome: a prospective interventional study.

BACKGROUND: Prone positioning in combination with the application of low tidal volume and adequate positive end-expiratory pressure (PEEP) improves survival in patients with moderate to severe acute respiratory distress syndrome (ARDS). However, the effects of PEEP on end-expiratory transpulmonary pressure (Ptpexp) during prone positioning require clarification. For this purpose, the effects of three different PEEP titration strategies on Ptpexp, respiratory mechanics, mechanical power, gas exchange, and hemodynamics were evaluated comparing supine and prone positioning. METHODS: In forty consecutive patients with moderate to severe ARDS protective ventilation with PEEP titrated according to three different titration strategies was evaluated during supine and prone positioning: (A) ARDS Network recommendations (PEEPARDSNetwork), (B) the lowest static elastance of the respiratory system (PEEPEstat,RS), and (C) targeting a positive Ptpexp (PEEPPtpexp). The primary endpoint was to analyze whether Ptpexp differed significantly according to PEEP titration strategy during supine and prone positioning. RESULTS: Ptpexp increased progressively with prone positioning compared with supine positioning as well as with PEEPEstat,RS and PEEPPtpexp compared with PEEPARDSNetwork (positioning effect p < 0.001, PEEP strategy effect p < 0.001). PEEP was lower during prone positioning with PEEPEstat,RS and PEEPPtpexp (positioning effect p < 0.001, PEEP strategy effect p < 0.001). During supine positioning, mechanical power increased progressively with PEEPEstat,RS and PEEPPtpexp compared with PEEPARDSNetwork, and prone positioning attenuated this effect (positioning effect p < 0.001, PEEP strategy effect p < 0.001). Prone compared with supine positioning significantly improved oxygenation (positioning effect p < 0.001, PEEP strategy effect p < 0.001) while hemodynamics remained stable in both positions. CONCLUSIONS: Prone positioning increased transpulmonary pressures while improving oxygenation and hemodynamics in patients with moderate to severe ARDS when PEEP was titrated according to the ARDS Network lower PEEP table. This PEEP titration strategy minimized parameters associated with ventilator-induced lung injury induction, such as transpulmonary driving pressure and mechanical power. We propose that a lower PEEP strategy (PEEPARDSNetwork) in combination with prone positioning may be part of a lung protective ventilation strategy in patients with moderate to severe ARDS. TRIAL REGISTRATION: German Clinical Trials Register ( DRKS00017449 ). Registered June 27, 2019. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00017449.

Procollagen I and III as Prognostic Markers in Patients Treated with Extracorporeal Membrane Oxygenation: A Prospective Observational Study.

Background: Procollagen peptides have been associated with lung fibroproliferation and poor outcomes in patients with acute respiratory distress syndrome (ARDS). Therefore, serum procollagen concentrations might have prognostic value in ARDS patients treated with extracorporeal membrane oxygenation (ECMO). Methods: In a prospective cohort study, serum N-terminal procollagen I-peptide (PINP) and N-terminal procollagen III-peptide (PIIINP) concentrations in twenty-three consecutive patients with severe ARDS treated with ECMO were measured at the time of ECMO initiation and during the course of treatment. The predictive value of PINP and PIIINP at the time of ECMO initiation was tested with a univariable logistic regression and a receiver operating characteristic (ROC) curve analysis. Results: Thirteen patients survived to intensive care unit (ICU) discharge. Non-survivors had higher serum PINP and PIIINP concentrations at all points in time during the course of treatment. Serum PIIINP at the day of ECMO initiation showed an odds ratio of 1.37 (95% CI 1.10-1.89, p = 0.017) with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.87 (95% CI 0.69-1.00, p = 0.0029) for death during the course of treatment. Conclusions: PINP and PIIINP concentrations differ between survivors and non-survivors in ARDS treated with ECMO. This exploratory hypothesis generating study suggests an association between PIIINP serum concentrations at ECMO initiation and an unfavorable clinical outcome.

Transpulmonary thermodilution in patients treated with veno-venous extracorporeal membrane oxygenation.

BACKGROUND: We tested the effect of different blood flow levels in the extracorporeal circuit on the measurements of cardiac stroke volume (SV), global end-diastolic volume index (GEDVI) and extravascular lung water index derived from transpulmonary thermodilution (TPTD) in 20 patients with severe acute respiratory distress syndrome (ARDS) treated with veno-venous extracorporeal membrane oxygenation (ECMO). METHODS: Comparative SV measurements with transesophageal echocardiography and TPTD were performed at least 5 times during the treatment of the patients. The data were interpreted with a Bland-Altman analysis corrected for repeated measurements. The interchangeability between both measurement modalities was calculated and the effects of extracorporeal blood flow on SV measurements with TPTD was analysed with a linear mixed effect model. GEDVI and EVLWI measurements were performed immediately before the termination of the ECMO therapy at a blood flow of 6 l/min, 4 l/min and 2 l/min and after the disconnection of the circuit in 7 patients. RESULTS: 170 pairs of comparative SV measurements were analysed. Average difference between the two modalities (bias) was 0.28 ml with an upper level of agreement of 40 ml and a lower level of agreement of -39 ml within a 95% confidence interval and an overall interchangeability rate between TPTD and Echo of 64%. ECMO blood flow did not influence the mean bias between Echo and TPTD (0.03 ml per l/min of ECMO blood flow; p = 0.992; CI - 6.74 to 6.81). GEDVI measurement was not significantly influenced by the blood flow in the ECMO circuit, whereas EVLWI differed at a blood flow of 6 l/min compared to no ECMO flow (25.9 ± 10.1 vs. 11.0 ± 4.2 ml/kg, p = 0.0035). CONCLUSIONS: Irrespectively of an established ECMO therapy, comparative SV measurements with Echo and TPTD are not interchangeable. Such caveats also apply to the interpretation of EVLWI, especially with a high blood flow in the extracorporeal circulation. In such situations, the clinician should rely on other methods of evaluation of the amount of lung oedema with the haemodynamic situation, vasopressor support and cumulative fluid balance in mind. TRIAL REGISTRATION: German Clinical Trials Register (DRKS00021050). Registered 03/30/2020 https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00017237.

Water Consumption during a School Day and Children's Short-Term Cognitive Performance: The CogniDROP Randomized Intervention Trial.

There is still little research examining the relationship between water consumption in school and specific cognitive performance. The aim of this cluster-randomized intervention CogniDROP trial was to investigate the short-term effects of drinking water during the morning on executive functions. The participants were from the 5th and 6th grade of a comprehensive school in Germany (14 classes, n = 250, 61.6% boys). The classes were randomly divided into an intervention group (an education on healthy drinking behavior and a promotion of water consumption) and a control group. A battery of computerized tasks (Switch Task, 2-Back Task, Corsi Block-Tapping Task and Flanker Task) was used to test executive functions. Urine color and thirst were evaluated to check the hydration level. Physical activity over the past 24 h was measured using GT3X ActiGraph. A non-linear relationship was observed between the amount of drinking water and executive performance. Consuming water up to 1000 mL (or up to 50% of Total Water Intake) had benefits during memory tasks. Urine color and number of steps on the study day correlated with water consumed. The results suggest that a water-friendly environment supports school-aged children in adequate water intake resulting in better cognitive performance, especially short-term memory.

Positive end-expiratory pressure titrated according to respiratory system mechanics or to ARDSNetwork table did not guarantee positive end-expiratory transpulmonary pressure in acute respiratory distress syndrome.

PURPOSE: Pulmonary recruitment and positive end-expiratory pressure (PEEP) titrated according to minimal static elastance of the respiratory system (PEEPEstat,RS) compared to PEEP set according to the ARDSNetwork table (PEEPARDSNetwork) as a strategy to prevent ventilator-associated lung injury (VALI) in patients with acute respiratory distress syndrome (ARDS) increases mortality. Alternatively, avoiding negative end-expiratory transpulmonary pressure has been discussed as superior PEEP titration strategy. Therefore, we tested whether PEEPEstat,RS or PEEPARDSNetwork prevent negative end-expiratory transpulmonary pressure in ARDS patients. MATERIAL AND METHODS: Thirteen patients with moderate to severe ARDS were studied at PEEPARDSNetwork versus PEEPEstat,RS. Patients were then grouped post hoc according to the end-expiratory transpulmonary pressure (positive or negative). RESULTS: 7 out of 13 patients showed negative end-expiratory transpulmonary pressures (Ptp-) with both strategies (PEEPARDSNetwork: - 5.4 ±â€¯3.5 vs. 2.2 ±â€¯3.7 cm H2O, p = .005; PEEPEstat,RS: - 3.6 ±â€¯1.5 vs. 3.5 ±â€¯3.3 cm H2O, p < .001). Ptp- was associated with higher intra-abdominal pressure and lower end-expiratory lung volume with both PEEP strategies. CONCLUSIONS: In patients with moderate-to-severe ARDS, PEEP titrated according to the minimal static elastance of the respiratory system or according to the ARDSNetwork table did not prevent negative end-expiratory transpulmonary pressure.

Regeneration of the entire human epidermis using transgenic stem cells.

Junctional epidermolysis bullosa (JEB) is a severe and often lethal genetic disease caused by mutations in genes encoding the basement membrane component laminin-332. Surviving patients with JEB develop chronic wounds to the skin and mucosa, which impair their quality of life and lead to skin cancer. Here we show that autologous transgenic keratinocyte cultures regenerated an entire, fully functional epidermis on a seven-year-old child suffering from a devastating, life-threatening form of JEB. The proviral integration pattern was maintained in vivo and epidermal renewal did not cause any clonal selection. Clonal tracing showed that the human epidermis is sustained not by equipotent progenitors, but by a limited number of long-lived stem cells, detected as holoclones, that can extensively self-renew in vitro and in vivo and produce progenitors that replenish terminally differentiated keratinocytes. This study provides a blueprint that can be applied to other stem cell-mediated combined ex vivo cell and gene therapies.

Effects of mechanical ventilation on gene expression profiles in renal allografts from brain dead rats.

Pathophysiological changes of brain death (BD) are impairing distal organ function and harming potential renal allografts. Whether ventilation strategies influence the quality of renal allografts from BD donors has not been thoroughly studied. 28 adult male Wistar rats were randomly assigned to four groups: 1) no brain death (NBD) with low tidal volume/low positive endexpiratory pressure (PEEP) titrated to minimal static elastance of the respiratory system (LVT/OLPEEP); 2) NBD with high tidal volume/low PEEP (HVT/LPEEP); 3) brain death (BD) with LVT/OLPEEP; and 4) BD with HVT/LPEEP. We hypothesized that HVT/LPEEP in BD leads to increased interleukin 6 (IL-6) gene expression and impairs potential renal allografts after six hours of mechanical ventilation. We assessed inflammatory cytokines in serum, genome wide gene expression profiles and quantitative PCR (qPCR) in kidney tissue. The influence of BD on renal gene-expression profiles was greater than the influence of the ventilation strategy. In BD, LVT ventilation did not influence the inflammatory parameters or kidney function in our experimental model.

Effects of lipopolysaccharide-induced inflammation on initial lung fibrosis during open-lung mechanical ventilation in rats.

This study aimed to assess the impact of pulmonary inflammation on early fibrotic response in rats challenged with increasing doses of lipopolysaccharide (LPS). Twenty-four rats were randomized and infused with three different increasing doses of continuous LPS infusion (n=8/group) while being ventilated with low tidal volumes and open-lung positive end-expiratory pressure. Another eight animals served as uninjured control group. Hemodynamics, gas exchange, respiratory system mechanics, lung histology, α-smooth muscle actin, plasma cytokines, and mRNA expression of cytokines and type I and III procollagen in lung tissue were assessed. We found impaired hemodynamics and gas exchange as well as higher histological lung injury scores and α-smooth muscle actin expressions in the medium LPS dose compared to control and the lower LPS dose. The highest LPS dose did not cause further aggravation of these findings. In all LPS groups type I and III procollagen decreased compared to controls and there was a negative correlation between type III procollagen-RNA expression and proinflammatory mediators.

Open lung approach with low tidal volume mechanical ventilation attenuates lung injury in rats with massive brain damage.

INTRODUCTION: The ideal ventilation strategy for patients with massive brain damage requires better elucidation. We hypothesized that in the presence of massive brain injury, a ventilation strategy using low (6 milliliters per kilogram ideal body weight) tidal volume (V(T)) ventilation with open lung positive end-expiratory pressure (LV(T)/OLPEEP) set according to the minimal static elastance of the respiratory system, attenuates the impact of massive brain damage on gas-exchange, respiratory mechanics, lung histology and whole genome alterations compared with high (12 milliliters per kilogram ideal body weight) V(T) and low positive end-expiratory pressure ventilation (HV(T)/LPEEP). METHODS: In total, 28 adult male Wistar rats were randomly assigned to one of four groups: 1) no brain damage (NBD) with LV(T)/OLPEEP; 2) NBD with HV(T)/LPEEP; 3) brain damage (BD) with LV(T)/OLPEEP; and 4) BD with HV9T)/LPEEP. All animals were mechanically ventilated for six hours. Brain damage was induced by an inflated balloon catheter into the epidural space. Hemodynamics was recorded and blood gas analysis was performed hourly. At the end of the experiment, respiratory system mechanics and lung histology were analyzed. Genome wide gene expression profiling and subsequent confirmatory quantitative polymerase chain reaction (qPCR) for selected genes were performed. RESULTS: In NBD, both LV(T)/OLPEEP and HV(T)/LPEEP did not affect arterial blood gases, as well as whole genome expression changes and real-time qPCR. In BD, LVT/OLPEEP, compared to HV(T)/LPEEP, improved oxygenation, reduced lung damage according to histology, genome analysis and real-time qPCR with decreased interleukin 6 (IL-6), cytokine-induced neutrophil chemoattractant 1 (CINC)-1 and angiopoietin-4 expressions. LV(T)/OLPEEP compared to HV(T)/LPEEP improved overall survival. CONCLUSIONS: In BD, LV(T)/OLPEEP minimizes lung morpho-functional changes and inflammation compared to HV(T)/LPEEP.

Lung imaging for titration of mechanical ventilation.

PURPOSE OF REVIEW: Computed tomography (CT) has fostered pivotal advancements in the understanding of acute lung injury/acute respiratory distress syndrome and ventilator-induced lung injury. Apart from CT-based studies, the past years have seen fascinating work using positron emission tomography, electrical impedance tomography and lung ultrasound as diagnostic tools to optimize mechanical ventilation. This review aims to present the major findings of recent studies on lung imaging. RECENT FINDINGS: Patients presenting with a focal loss of aeration on CT may not be suitable candidates for recruitment maneuvers and high levels of positive end-expiratory pressure (PEEP) in supine position. PET/CT has provided valuable insights into the inflammatory response of the lung. Electrical impedance tomography has been used to assess lung recruitability and to titrate PEEP. Finally, lung ultrasound has proven to be reliable diagnostic tool for assessing PEEP-induced recruitment. SUMMARY: Whereas quantitative CT remains the gold standard to assess lung morphology, recruitment and hyperinflation of lung tissue at different inflation pressures, EIT and LUS have emerged as valuable, radiation-free, noninvasive bedside lung imaging tools that should be used together with global parameters like lung mechanics and gas exchange to acquire additional information on recruitability and ventilation distribution.

Time course of lung inflammatory and fibrogenic responses during protective mechanical ventilation in healthy rats.

This study aimed to assess pulmonary inflammatory and fibrogenic responses and their impact on lung mechanics and histology in healthy rats submitted to protective mechanical ventilation for different experimental periods. Eighteen Wistar rats were randomized to undergo open lung-mechanical ventilation (OL-MV) for 1, 6 or 12 h. Following a recruitment maneuver, a decremental PEEP trial was performed and PEEP set according to the minimal respiratory system static elastance. Respiratory system, lung, and chest-wall elastance and gas-exchange were maintained throughout the 12 h experimental period. Histological lung injury score remained low at 1 and 6 h, but was higher at 12 h due to overinflation. A moderate inflammatory response was observed with a distinct peak at 6h. Compared to unventilated controls, type I procollagen mRNA expression was decreased at 1 and 12h, while type III procollagen expression decreased throughout the 12h experimental period. In conclusion, OL-MV in healthy rats yielded overinflation after 6 h even though respiratory elastance and gas-exchange were preserved for up to 12 h.

Chest wall mechanics and abdominal pressure during general anaesthesia in normal and obese individuals and in acute lung injury.

PURPOSE OF REVIEW: This article discusses the methods available to evaluate chest wall mechanics and the relationship between intraabdominal pressure (IAP) and chest wall mechanics during general anaesthesia in normal and obese individuals, as well as in acute lung injury/acute respiratory distress syndrome. RECENT FINDINGS: The interactions between the abdominal and thoracic compartments pose a specific challenge for intensive care physicians. IAP affects respiratory system, lung and chest wall elastance in an unpredictable way. Thus, transpulmonary pressure should be measured if IAP is more than 12 mmHg or if chest wall elastance is compromised for other reasons, even though the absolute values of pleural and transpulmonary pressures are not easily obtained at bedside. We suggest defining intraabdominal hypertension (IAH) as IAP at least 20 mmHg and abdominal compartment syndrome (ACS) as IAP at least 20 mmHg associated with failure of one or more organs, although further studies are required to confirm this hypothesis. Additionally, in the presence of IAH, controlled mechanical ventilation should be applied and positive end-expiratory pressure individually titrated. Prophylactic open abdomen should be considered in the presence of ACS. SUMMARY: Increased IAP markedly affects respiratory function and complicates patient management. Frequent assessment of IAP is recommended.