Early administration of umbilical cord blood cells following brief high tidal volume ventilation in preterm sheep: a cautionary tale.

BACKGROUND: Umbilical cord blood (UCB) cells are a promising treatment for preterm brain injury. Access to allogeneic sources of UCB cells offer the potential for early administration to optimise their therapeutic capacities. As preterm infants often require ventilatory support, which can contribute to preterm brain injury, we investigated the efficacy of early UCB cell administration following ventilation to reduce white matter inflammation and injury. METHODS: Preterm fetal sheep (0.85 gestation) were randomly allocated to no ventilation (SHAM; n = 5) or 15 min ex utero high tidal volume ventilation. One hour following ventilation, fetuses were randomly allocated to i.v. administration of saline (VENT; n = 7) or allogeneic term-derived UCB cells (24.5 ± 5.0 million cells/kg; VENT + UCB; n = 7). Twenty-four hours after ventilation, lambs were delivered for magnetic resonance imaging and post-mortem brain tissue collected. Arterial plasma was collected throughout the experiment for cytokine analyses. To further investigate the results from the in vivo study, mononuclear cells (MNCs) isolated from human UCB were subjected to in vitro cytokine-spiked culture medium (TNFα and/or IFNγ; 10 ng/mL; n = 3/group) for 16 h then supernatant and cells collected for protein and mRNA assessments respectively. RESULTS: In VENT + UCB lambs, systemic IFNγ levels increased and by 24 h, there was white matter neuroglial activation, vascular damage, reduced oligodendrocytes, and increased average, radial and mean diffusivity compared to VENT and SHAM. No evidence of white matter inflammation or injury was present in VENT lambs, except for mRNA downregulation of OCLN and CLDN1 compared to SHAM. In vitro, MNCs subjected to TNFα and/or IFNγ displayed both pro- and anti-inflammatory characteristics indicated by changes in cytokine (IL-18 & IL-10) and growth factor (BDNF & VEGF) gene and protein expression compared to controls. CONCLUSIONS: UCB cells administered early after brief high tidal volume ventilation in preterm fetal sheep causes white matter injury, and the mechanisms underlying these changes are likely dysregulated responses of the UCB cells to the degree of injury/inflammation already present. If immunomodulatory therapies such as UCB cells are to become a therapeutic strategy for preterm brain injury, especially after ventilation, our study suggests that the inflammatory state of the preterm infant should be considered when timing UCB cells administration.

Breath-by-breath comparison of a novel percutaneous phrenic nerve stimulation approach with mechanical ventilation in juvenile pigs: a pilot study.

About one in three critically ill patients requires mechanical ventilation (MV). Prolonged MV, however, results in diaphragmatic weakness, which itself is associated with delayed weaning and increased mortality. Inducing active diaphragmatic contraction via electrical phrenic nerve stimulation (PNS) not only provides the potential to reduce diaphragmatic muscular atrophy but also generates physiological-like ventilation and therefore offers a promising alternative to MV. Reasons why PNS is not yet used in critical care medicine are high procedural invasiveness, insufficient evidence, and lack of side-by-side comparison to MV. This study aims to establish a minimal-invasive percutaneous, bilateral electrode placement approach for sole PNS breathing and thereby enable, for the first time, a breath-by-breath comparison to MV. Six juvenile German Landrace pigs received general anesthesia and orotracheal intubation. Following the novel ultrasound-guided, landmark-based, 4-step approach, two echogenic needles per phrenic nerve were successfully placed. Stimulation effectiveness was evaluated measuring tidal volume, diaphragmatic thickening and tomographic electrical impedance in a breath-by-breath comparison to MV. Following sufficient bilateral phrenic nerve stimulation in all pigs, PNS breaths showed a 2.2-fold increase in diaphragmatic thickening. It induced tidal volumes in the lung-protective range by negative pressure inspiration and improved dorso-caudal regional ventilation in contrast to MV. Our study demonstrated the feasibility of a novel ultrasound-guided, percutaneous phrenic nerve stimulation approach, which generated sufficient tidal volumes and showed more resemblance to physiological breathing than MV in a breath-by-breath comparison.

[Small tidal volume hyperventilation relieves intraocular and intracranial pressure elevation in prone spinal surgery: a randomized controlled trial].

OBJECTIVE: To investigate the effects of different ventilation strategies on intraocular pressure (IOP) and intracranial pressure in patients undergoing spinal surgery in the prone position under general anesthesia. METHODS: Seventy-two patients undergoing prone spinal surgery under general anesthesia between November, 2022 and June, 2023 were equally randomized into two groups to receive routine ventilation (with Vt of 8mL/kg, Fr of 12-15/min, and etCO2 maintained at 35-40 mmHg) or small tidal volume hyperventilation (Vt of 6 mL/kg, Fr of18-20/min, and etCO2 maintained at 30-35 mmHg) during the surgery. IOP of both eyes (measured with a handheld tonometer), optic nerve sheath diameter (ONSD; measured at 3 mm behind the eyeball with bedside real-time ultrasound), circulatory and respiratory parameters of the patients were recorded before anesthesia (T0), immediately after anesthesia induction (T1), immediately after prone positioning (T2), at 2 h during operation (T3), immediately after supine positioning after surgery (T4) and 30 min after the operation (T5). RESULTS: Compared with those at T1, IOP and ONSD in both groups increased significantly at T3 and T4(P < 0.05). IOP was significantly lower in hyperventilation group than in routine ventilation group at T3 and T4(P < 0.05), and ONSD was significantly lower in hyperventilation group at T4(P < 0.05). IOP was positively correlated with the length of operative time (r=0.779, P < 0.001) and inversely with intraoperative etCO2 at T3(r=-0.248, P < 0.001) and T4(r=-0.251, P < 0.001).ONSD was correlated only with operation time (r=0.561, P < 0.05) and not with IOP (r=0.178, P>0.05 at T3; r=0.165, P>0.05 at T4). CONCLUSION: Small tidal volume hyperventilation can relieve the increase of IOP and ONSD during prone spinal surgery under general anesthesia.

Continuous estimation of respiratory system compliance and airway resistance during pressure-controlled ventilation without end-inspiration occlusion.

BACKGROUND: Assessing mechanical properties of the respiratory system (Cst) during mechanical ventilation necessitates an end-inspiration flow of zero, which requires an end-inspiratory occlusion maneuver. This lung model study aimed to observe the effect of airflow obstruction on the accuracy of respiratory mechanical properties during pressure-controlled ventilation (PCV) by analyzing dynamic signals. METHODS: A Hamilton C3 ventilator was attached to a lung simulator that mimics lung mechanics in healthy, acute respiratory distress syndrome (ARDS) and chronic obstructive pulmonary disease (COPD) models. PCV and volume-controlled ventilation (VCV) were applied with tidal volume (VT) values of 5.0, 7.0, and 10.0 ml/kg. Performance characteristics and respiratory mechanics were assessed and were calibrated by virtual extrapolation using expiratory time constant (RCexp). RESULTS: During PCV ventilation, drive pressure (DP) was significantly increased in the ARDS model. Peak inspiratory flow (PIF) and peak expiratory flow (PEF) gradually declined with increasing severity of airflow obstruction, while DP, end-inspiration flow (EIF), and inspiratory cycling ratio (EIF/PIF%) increased. Similar estimated values of Crs and airway resistance (Raw) during PCV and VCV ventilation were obtained in healthy adult and mild obstructive models, and the calculated errors did not exceed 5%. An underestimation of Crs and an overestimation of Raw were observed in the severe obstruction model. CONCLUSION: Using the modified dynamic signal analysis approach, respiratory system properties (Crs and Raw) could be accurately estimated in patients with non-severe airflow obstruction in the PCV mode.

Expiratory flow limitation during mechanical ventilation: real-time detection and physiological subtypes.

BACKGROUND: Tidal expiratory flow limitation (EFLT) complicates the delivery of mechanical ventilation but is only diagnosed by performing specific manoeuvres. Instantaneous analysis of expiratory resistance (Rex) can be an alternative way to detect EFLT without changing ventilatory settings. This study aimed to determine the agreement of EFLT detection by Rex analysis and the PEEP reduction manoeuvre using contingency table and agreement coefficient. The patterns of Rex were explored. METHODS: Medical patients ≥ 15-year-old receiving mechanical ventilation underwent a PEEP reduction manoeuvre from 5 cmH2O to zero for EFLT detection. Waveforms were recorded and analyzed off-line. The instantaneous Rex was calculated and was plotted against the volume axis, overlapped by the flow-volume loop for inspection. Lung mechanics, characteristics of the patients, and clinical outcomes were collected. The result of the Rex method was validated using a separate independent dataset. RESULTS: 339 patients initially enrolled and underwent a PEEP reduction. The prevalence of EFLT was 16.5%. EFLT patients had higher adjusted hospital mortality than non-EFLT cases. The Rex method showed 20% prevalence of EFLT and the result was 90.3% in agreement with PEEP reduction manoeuvre. In the validation dataset, the Rex method had resulted in 91.4% agreement. Three patterns of Rex were identified: no EFLT, early EFLT, associated with airway disease, and late EFLT, associated with non-airway diseases, including obesity. In early EFLT, external PEEP was less likely to eliminate EFLT. CONCLUSIONS: The Rex method shows an excellent agreement with the PEEP reduction manoeuvre and allows real-time detection of EFLT. Two subtypes of EFLT are identified by Rex analysis. TRIAL REGISTRATION: Clinical trial registered with www.thaiclinicaltrials.org (TCTR20190318003). The registration date was on 18 March 2019, and the first subject enrollment was performed on 26 March 2019.

Evaluation of the relationship between end-tidal carbon dioxide level and heart failure classification.

OBJECTIVE: Heart failure is a disease with cardiac dysfunction, and its morbidity and mortality are associated with the degree of dysfunction. The New York Heart Association classifies the heart failure stages based on the severity of symptoms and physical activity. End-tidal carbon dioxide refers to the level of carbon dioxide that a person exhales with each breath. End-tidal carbon dioxide levels can be used in many clinical conditions such as heart failure, asthma, and chronic obstructive pulmonary disease. The aim of the study was to reveal the relationship between end-tidal carbon dioxide levels and the New York Heart Association classification of heart failure stages. METHODS: This study was conducted at Kahramanmaras Sütçü Imam University Faculty of Medicine Adult Emergency Department between 01/03/2019 and 01/09/2019. A total of 80 patients who presented to the emergency department with a history of heart failure or were diagnosed with heart failure during admission were grouped according to the New York Heart Association classification of heart failure stages. The laboratory parameters, ejection fraction values, and end-tidal carbon dioxide levels of the patients were measured and recorded in the study forms. RESULTS: End-tidal carbon dioxide levels and ejection fraction values were found to be significantly lower in the stage 4 group compared to the other groups. Furthermore, pro-B-type natriuretic peptide (BNP) values were found to be significantly higher in stage 4 group compared to the other groups. CONCLUSION: It was concluded that end-tidal carbon dioxide levels could be used together with pro-BNP and ejection fraction values in determining the severity of heart failure.

Prospective, randomized, controlled trial assessing the effects of a driving pressure-limiting strategy for patients with acute respiratory distress syndrome due to community-acquired pneumonia (STAMINA trial): protocol and statistical analysis plan.

BACKGROUND: Driving pressure has been suggested to be the main driver of ventilator-induced lung injury and mortality in observational studies of acute respiratory distress syndrome. Whether a driving pressure-limiting strategy can improve clinical outcomes is unclear. OBJECTIVE: To describe the protocol and statistical analysis plan that will be used to test whether a driving pressure-limiting strategy including positive end-expiratory pressure titration according to the best respiratory compliance and reduction in tidal volume is superior to a standard strategy involving the use of the ARDSNet low-positive end-expiratory pressure table in terms of increasing the number of ventilator-free days in patients with acute respiratory distress syndrome due to community-acquired pneumonia. METHODS: The ventilator STrAtegy for coMmunIty acquired pNeumoniA (STAMINA) study is a randomized, multicenter, open-label trial that compares a driving pressure-limiting strategy to the ARDSnet low-positive end-expiratory pressure table in patients with moderate-to-severe acute respiratory distress syndrome due to community-acquired pneumonia admitted to intensive care units. We expect to recruit 500 patients from 20 Brazilian and 2 Colombian intensive care units. They will be randomized to a driving pressure-limiting strategy group or to a standard strategy using the ARDSNet low-positive end-expiratory pressure table. In the driving pressure-limiting strategy group, positive end-expiratory pressure will be titrated according to the best respiratory system compliance. OUTCOMES: The primary outcome is the number of ventilator-free days within 28 days. The secondary outcomes are in-hospital and intensive care unit mortality and the need for rescue therapies such as extracorporeal life support, recruitment maneuvers and inhaled nitric oxide. CONCLUSION: STAMINA is designed to provide evidence on whether a driving pressure-limiting strategy is superior to the ARDSNet low-positive end-expiratory pressure table strategy for increasing the number of ventilator-free days within 28 days in patients with moderate-to-severe acute respiratory distress syndrome. Here, we describe the rationale, design and status of the trial.

Driving pressure, as opposed to tidal volume based on predicted body weight, is associated with mortality: results from a prospective cohort of COVID-19 acute respiratory distress syndrome patients.

OBJECTIVE: To evaluate the association between driving pressure and tidal volume based on predicted body weight and mortality in a cohort of patients with acute respiratory distress syndrome caused by COVID-19. METHODS: This was a prospective, observational study that included patients with acute respiratory distress syndrome due to COVID-19 admitted to two intensive care units. We performed multivariable analyses to determine whether driving pressure and tidal volume/kg predicted body weight on the first day of mechanical ventilation, as independent variables, are associated with hospital mortality. RESULTS: We included 231 patients. The mean age was 64 (53 - 74) years, and the mean Simplified Acute and Physiology Score 3 score was 45 (39 - 54). The hospital mortality rate was 51.9%. Driving pressure was independently associated with hospital mortality (odds ratio 1.21, 95%CI 1.04 - 1.41 for each cm H2O increase in driving pressure, p = 0.01). Based on a double stratification analysis, we found that for the same level of tidal volume/kg predicted body weight, the risk of hospital death increased with increasing driving pressure. However, changes in tidal volume/kg predicted body weight were not associated with mortality when they did not lead to an increase in driving pressure. CONCLUSION: In patients with acute respiratory distress syndrome caused by COVID-19, exposure to higher driving pressure, as opposed to higher tidal volume/kg predicted body weight, is associated with greater mortality. These results suggest that driving pressure might be a primary target for lung-protective mechanical ventilation in these patients.

Development and performance evaluation of a solenoid valve assisted low-cost ventilator on gas exchange and respiratory mechanics in a porcine model.

INTRODUCTION: During the COVID-19 pandemic, ventilator shortages necessitated the development of new, low-cost ventilator designs. The fundamental requirements of a ventilator include precise gas delivery, rapid adjustments, durability, and user-friendliness, often achieved through solenoid valves. However, few solenoid-valve assisted low-cost ventilator (LCV) designs have been published, and gas exchange evaluation during LCV testing is lacking. This study describes the development and performance evaluation of a solenoid-valve assisted low-cost ventilator (SV-LCV) in vitro and in vivo, focusing on gas exchange and respiratory mechanics. METHODS: The SV-LCV, a fully open ventilator device, was developed with comprehensive hardware and design documentation, utilizing solenoid valves for gas delivery regulation. Lung simulator testing calibrated tidal volumes at specified inspiratory and expiratory times, followed by in vivo testing in a porcine model to compare SV-LCV performance with a conventional ventilator. RESULTS: The SV-LCV closely matched the control ventilator's respiratory profile and gas exchange across all test cycles. Lung simulator testing revealed direct effects of compliance and resistance changes on peak pressures and tidal volumes, with no significant changes in respiratory rate. In vivo testing demonstrated comparable gas exchange parameters between SV-LCV and conventional ventilator across all cycles. Specifically, in cycle 1, the SV-LCV showed arterial blood gas (ABG) results of pH 7.54, PCO2 34.5 mmHg, and PO2 91.7 mmHg, compared to the control ventilator's ABG of pH 7.53, PCO2 37.1 mmHg, and PO2 134 mmHg. Cycle 2 exhibited ABG results of pH 7.53, PCO2 33.6 mmHg, and PO2 84.3 mmHg for SV-LCV, and pH 7.5, PCO2 34.2 mmHg, and PO2 93.5 mmHg for the control ventilator. Similarly, cycle 3 showed ABG results of pH 7.53, PCO2 32.1 mmHg, and PO2 127 mmHg for SV-LCV, and pH 7.5, PCO2 35.5 mmHg, and PO2 91.3 mmHg for the control ventilator. CONCLUSION: The SV-LCV provides similar gas exchange and respiratory mechanic profiles compared to a conventional ventilator. With a streamlined design and performance akin to commercially available ventilators, the SV-LCV presents a viable, readily available, and reliable short-term solution for overcoming ventilator supply shortages during crises.

Comparison of limited driving pressure ventilation and low tidal volume strategies in adults with acute respiratory failure on mechanical ventilation: a randomized controlled trial.

BACKGROUND: Ventilator-induced lung injury (VILI) presents a grave risk to acute respiratory failure patients undergoing mechanical ventilation. Low tidal volume (LTV) ventilation has been advocated as a protective strategy against VILI. However, the effectiveness of limited driving pressure (plateau pressure minus positive end-expiratory pressure) remains unclear. OBJECTIVES: This study evaluated the efficacy of LTV against limited driving pressure in preventing VILI in adults with respiratory failure. DESIGN: A single-centre, prospective, open-labelled, randomized controlled trial. METHODS: This study was executed in medical intensive care units at Siriraj Hospital, Mahidol University, Bangkok, Thailand. We enrolled acute respiratory failure patients undergoing intubation and mechanical ventilation. They were randomized in a 1:1 allocation to limited driving pressure (LDP; ⩽15 cmH2O) or LTV (⩽8 mL/kg of predicted body weight). The primary outcome was the acute lung injury (ALI) score 7 days post-enrolment. RESULTS: From July 2019 to December 2020, 126 patients participated, with 63 each in the LDP and LTV groups. The cohorts had the mean (standard deviation) ages of 60.5 (17.6) and 60.9 (17.9) years, respectively, and they exhibited comparable baseline characteristics. The primary reasons for intubation were acute hypoxic respiratory failure (LDP 49.2%, LTV 63.5%) and shock-related respiratory failure (LDP 39.7%, LTV 30.2%). No significant difference emerged in the primary outcome: the median (interquartile range) ALI scores for LDP and LTV were 1.75 (1.00-2.67) and 1.75 (1.25-2.25), respectively (p = 0.713). Twenty-eight-day mortality rates were comparable: LDP 34.9% (22/63), LTV 31.7% (20/63), relative risk (RR) 1.08, 95% confidence interval (CI) 0.74-1.57, p = 0.705. Incidences of newly developed acute respiratory distress syndrome also aligned: LDP 14.3% (9/63), LTV 20.6% (13/63), RR 0.81, 95% CI 0.55-1.22, p = 0.348. CONCLUSIONS: In adults with acute respiratory failure, the efficacy of LDP and LTV in averting lung injury 7 days post-mechanical ventilation was indistinguishable. CLINICAL TRIAL REGISTRATION: The study was registered with the ClinicalTrials.gov database (identification number NCT04035915).

Limited breathing pressure or low amount of air given to the lung; which one is better for adults who need breathing help by ventilator machineWe conducted this research at Siriraj Hospital in Bangkok, Thailand, aiming to compare two ways of helping patients with breathing problems. We studied 126 patients who were randomly put into two groups. One group received a method where the pressure during breathing was limited (limited driving pressure: LDP), and the other group got a method where the amount of air given to the lungs was kept low (low tidal volume: LTV). We checked how bad the lung injury was at seven days later. The results showed that there was no difference between the two methods. Both ways of helping patients breathe had similar outcomes, and neither was significantly better than the other in preventing lung problems. The study suggests that both approaches work about the same for patients who need help with breathing using a machine.

Effect of the alveolar recruitment maneuver during laparoscopic colorectal surgery on postoperative pulmonary complications: A randomized controlled trial.

Intraoperative lung-protective ventilation, including low tidal volume and positive end-expiratory pressure, reduces postoperative pulmonary complications. However, the effect and specific alveolar recruitment maneuver method are controversial. We investigated whether the intraoperative intermittent recruitment maneuver further reduced postoperative pulmonary complications while using a lung-protective ventilation strategy. Adult patients undergoing elective laparoscopic colorectal surgery were randomly allocated to the recruitment or control groups. Intraoperative ventilation was adjusted to maintain a tidal volume of 6-8 mL kg-1 and positive end-expiratory pressure of 5 cmH2O in both groups. The alveolar recruitment maneuver was applied at three time points (at the start and end of the pneumoperitoneum, and immediately before extubation) by maintaining a continuous pressure of 30 cmH2O for 30 s in the recruitment group. Clinical and radiological evidence of postoperative pulmonary complications was investigated within 7 days postoperatively. A total of 125 patients were included in the analysis. The overall incidence of postoperative pulmonary complications was not significantly different between the recruitment and control groups (28.1% vs. 31.1%, P = 0.711), while the mean ±â€…standard deviation intraoperative peak inspiratory pressure was significantly lower in the recruitment group (10.7 ±â€…3.2 vs. 13.5 ±â€…3.0 cmH2O at the time of CO2 gas-out, P < 0.001; 9.8 ±â€…2.3 vs. 12.5 ±â€…3.0 cmH2O at the time of recovery, P < 0.001). The alveolar recruitment maneuver with a pressure of 30 cmH2O for 30 s did not further reduce postoperative pulmonary complications when a low tidal volume and 5 cmH2O positive end-expiratory pressure were applied to patients undergoing laparoscopic colorectal surgery and was not associated with any significant adverse events. However, the alveolar recruitment maneuver significantly reduced intraoperative peak inspiratory pressure. Further study is needed to validate the beneficial effect of the alveolar recruitment maneuver in patients at increased risk of postoperative pulmonary complications. Trial registration: Clinicaltrials.gov (NCT03681236).

Early pathophysiology-driven airway pressure release ventilation versus low tidal volume ventilation strategy for patients with moderate-severe ARDS: study protocol for a randomized, multicenter, controlled trial.

BACKGROUND: Conventional Mechanical ventilation modes used for individuals suffering from acute respiratory distress syndrome have the potential to exacerbate lung injury through regional alveolar overinflation and/or repetitive alveolar collapse with shearing, known as atelectrauma. Animal studies have demonstrated that airway pressure release ventilation (APRV) offers distinct advantages over conventional mechanical ventilation modes. However, the methodologies for implementing APRV vary widely, and the findings from clinical studies remain controversial. This study (APRVplus trial), aims to assess the impact of an early pathophysiology-driven APRV ventilation approach compared to a low tidal volume ventilation (LTV) strategy on the prognosis of patients with moderate to severe ARDS. METHODS: The APRVplus trial is a prospective, multicenter, randomized clinical trial, building upon our prior single-center study, to enroll 840 patients from at least 35 hospitals in China. This investigation plans to compare the early pathophysiology-driven APRV ventilation approach with the control intervention of LTV lung-protective ventilation. The primary outcome measure will be all-cause mortality at 28 days after randomization in the intensive care units (ICU). Secondary outcome measures will include assessments of oxygenation, and physiology parameters at baseline, as well as on days 1, 2, and 3. Additionally, clinical outcomes such as ventilator-free days at 28 days, duration of ICU and hospital stay, ICU and hospital mortality, and the occurrence of adverse events will be evaluated. TRIAL ETHICS AND DISSEMINATION: The research project has obtained approval from the Ethics Committee of West China Hospital of Sichuan University (2019-337). Informed consent is required. The results will be submitted for publication in a peer-reviewed journal and presented at one or more scientific conferences. TRIAL REGISTRATION: The study was registered at Clinical Trials.gov (NCT03549910) on June 8, 2018.

Adjustment of positive end-expiratory pressure to body mass index during mechanical ventilation in general anesthesia: BodyVent, a randomized controlled trial.

BACKGROUND: In patients requiring general anesthesia, lung-protective ventilation can prevent postoperative pulmonary complications, which are associated with higher morbidity, mortality, and prolonged hospital stay. Application of positive end-expiratory pressure (PEEP) is one component of lung-protective ventilation. The correct strategy for setting adequate PEEP, however, remains controversial. PEEP settings that lead to a lower pressure difference between end-inspiratory plateau pressure and end-expiratory pressure ("driving pressure," ΔP) may reduce the risk of postoperative pulmonary complications. Preliminary data suggests that the PEEP required to prevent both end-inspiratory overdistension and end-expiratory alveolar collapse, thereby reducing ΔP, correlates positively with the body mass index (BMI) of patients, with PEEP values corresponding to approximately 1/3 of patient's respective BMI. Thus, we hypothesize that adjusting PEEP according to patient BMI reduces ΔP and may result in less postoperative pulmonary complications. METHODS: Patients undergoing general anesthesia and endotracheal intubation with volume-controlled ventilation with a tidal volume of 7 ml per kg predicted body weight will be randomized and assigned to either an intervention group with PEEP adjusted according to BMI or a control group with a standardized PEEP of 5 mbar. Pre- and postoperatively, lung ultrasound will be performed to determine the lung aeration score, and hemodynamic and respiratory vital signs will be recorded for subsequent evaluation. The primary outcome is the difference in ΔP as a surrogate parameter for lung-protective ventilation. Secondary outcomes include change in lung aeration score, intraoperative occurrence of hemodynamic and respiratory events, oxygen requirements and postoperative pulmonary complications. DISCUSSION: The study results will show whether an intraoperative ventilation strategy with PEEP adjustment based on BMI has the potential of reducing the risk for postoperative pulmonary complications as an easy-to-implement intervention that does not require lengthy ventilator maneuvers nor additional equipment. TRIAL REGISTRATION: German Clinical Trials Register (DRKS), DRKS00031336. Registered 21st February 2023. TRIAL STATUS: The study protocol was approved by the ethics committee of the Christian-Albrechts-Universität Kiel, Germany, on 1st February 2023. Recruitment began in March 2023 and is expected to end in September 2023.

Obesity-related reduced spirometry and altered breathing pattern are associated with mechanical disadvantage of the diaphragm.

The aim of this study was to characterize the breathing patterns of individuals with obesity during routine activities such as sitting and standing, and to identify potential contributors to alterations in these patterns. Measurements performed in 20 male subjects with obesity (BMI, 31.8±1.5 kg/m2) and 20 controls (BMI, 23.5±1.4 kg/m2) included anthropometric parameters, breathing-patterns in sitting and standing positions, spirometry, maximal respiratory pressures, and diaphragm B-mode ultrasonography. Individuals with obesity exhibited lower tidal volume and increased respiratory rate to maintain a similar minute-ventilation (p<0.05). Subjects with obesity demonstrated impaired spirometry and respiratory muscle strength, with inspiratory functions being notably compromised (p<0.05). Individuals with obesity had a greater diaphragm thickness at end inspiration but lower thickening-fraction at end quiet and forced breathings and reduced diaphragmatic displacement and excursion during maximal breaths (p<0.05). BMI was negatively associated with all respiratory function markers (p<0.05). Individuals with obesity exhibit a higher respiratory rate but lower tidal volume, likely to accommodate decreased compliance and excess thoracic and abdominal fat, further hindering inspiratory function. Moreover, increased adiposity is associated with a thicker but weaker diaphragm, primarily due to the diaphragm's mechanical disadvantage rather than its intrinsic inability to generate force.

One-lung ventilation with fixed and variable tidal volumes on oxygenation and pulmonary outcomes: A randomized trial.

OBJECTIVE: Test the hypothesis that one-lung ventilation with variable tidal volume improves intraoperative oxygenation and reduces postoperative pulmonary complications after lung resection. BACKGROUND: Constant tidal volume and respiratory rate ventilation can lead to atelectasis. Animal and human ARDS studies indicate that oxygenation improves with variable tidal volumes. Since one-lung ventilation shares characteristics with ARDS, we tested the hypothesis that one-lung ventilation with variable tidal volume improves intraoperative oxygenation and reduces postoperative pulmonary complications after lung resection. DESIGN: Randomized trial. SETTING: Operating rooms and a post-anesthesia care unit. PATIENTS: Adults having elective open or video-assisted thoracoscopic lung resection surgery with general anesthesia were randomly assigned to intraoperative ventilation with fixed (n = 70) or with variable (n = 70) tidal volumes. INTERVENTIONS: Patients assigned to fixed ventilation had a tidal volume of 6 ml/kgPBW, whereas those assigned to variable ventilation had tidal volumes ranging from 6 ml/kg PBW ± 33% which varied randomly at 5-min intervals. MEASUREMENTS: The primary outcome was intraoperative oxygenation; secondary outcomes were postoperative pulmonary complications, mortality within 90 days of surgery, heart rate, and SpO2/FiO2 ratio. RESULTS: Data from 128 patients were analyzed with 65 assigned to fixed-tidal volume ventilation and 63 to variable-tidal volume ventilation. The time-weighted average PaO2 during one-lung ventilation was 176 (86) mmHg in patients ventilated with fixed-tidal volume and 147 (72) mmHg in the patients ventilated with variable-tidal volume, a difference that was statistically significant (p < 0.01) but less than our pre-defined clinically meaningful threshold of 50 mmHg. At least one composite complication occurred in 11 (17%) of patients ventilated with variable-tidal volume and in 17 (26%) of patients assigned to fixed-tidal volume ventilation, with a relative risk of 0.67 (95% CI 0.34-1.31, p = 0.24). Atelectasis in the ventilated lung was less common with variable-tidal volumes (4.7%) than fixed-tidal volumes (20%) in the initial three postoperative days, with a relative risk of 0.24 (95% CI 0.01-0.8, p = 0.02), but there were no significant late postoperative differences. No other secondary outcomes were both statistically significant and clinically meaningful. CONCLUSION: One-lung ventilation with variable tidal volume does not meaningfully improve intraoperative oxygenation, and does not reduce postoperative pulmonary complications.

Comparative effects of variable versus conventional volume-controlled one-lung ventilation on gas exchange and respiratory system mechanics in thoracic surgery patients: A randomized controlled clinical trial.

BACKGROUND: Mechanical ventilation with variable tidal volumes (V-VCV) has the potential to improve lung function during general anesthesia. We tested the hypothesis that V-VCV compared to conventional volume-controlled ventilation (C-VCV) would improve intraoperative arterial oxygenation and respiratory system mechanics in patients undergoing thoracic surgery under one-lung ventilation (OLV). METHODS: Patients were randomized to V-VCV (n = 39) or C-VCV (n = 39). During OLV tidal volume of 5 mL/kg predicted body weight (PBW) was used. Both groups were ventilated with a positive end-expiratory pressure (PEEP) of 5 cm H2O, inspiration to expiration ratio (I:E) of 1:1 (during OLV) and 1:2 during two-lung ventilation, the respiratory rate (RR) titrated to arterial pH, inspiratory peak-pressure ≤ 40 cm H2O and an inspiratory oxygen fraction of 1.0. RESULTS: Seventy-five out of 78 Patients completed the trial and were analyzed (dropouts were excluded). The partial pressure of arterial oxygen (PaO2) 20 min after the start of OLV did not differ among groups (V-VCV: 25.8 ± 14.6 kPa vs C-VCV: 27.2 ± 15.3 kPa; mean difference [95% CI]: 1.3 [-8.2, 5.5], P = 0.700). Furthermore, intraoperative gas exchange, intraoperative adverse events, need for rescue maneuvers due to desaturation and hypercapnia, incidence of postoperative pulmonary and extra-pulmonary complications, and hospital free days at day 30 after surgery did not differ between groups. CONCLUSIONS: In thoracic surgery patients under OLV, V-VCV did not improve oxygenation or respiratory system mechanics compared to C-VCV. Ethical Committee: EK 420092019. TRIAL REGISTRATION: at the German Clinical Trials Register: DRKS00022202 (16.06.2020).

Contribution of electrical impedance tomography to personalize positive end-expiratory pressure under ECCO2R.

Extracorporeal Carbon Dioxide Removal (ECCO2R) is used in acute respiratory distress syndrome (ARDS) patients to facilitate lung-protective ventilatory strategies. Electrical Impedance Tomography (EIT) allows individual, non-invasive, real-time, bedside, radiation-free imaging of the lungs, providing global and regional dynamic lung analyses. To provide new insights for future ECCO2R research in ARDS, we propose a potential application of EIT to personalize End-Expiratory Pressure (PEEP) following each reduction in tidal volume (VT), as demonstrated in an illustrative case. A 72-year-old male with COVID-19 was admitted to the ICU for moderate ARDS. Monitoring with EIT was started to determine the optimal PEEP value (PEEPEIT), defined as the intersection of the collapse and overdistention curves, after each reduction in VT during ECCO2R. The identified PEEPEIT values were notably low (< 10 cmH2O). The decrease in VT associated with PEEPEIT levels resulted in improved lung compliance, reduced driving pressure and a more uniform ventilation pattern. Despite current Randomized Controlled Trials showing that ultra-protective ventilation with ECCO2R does not improve survival, the applicability of universal ultra-protective ventilation settings for all patients remains a subject of debate. Inappropriately set PEEP levels can lead to alveolar collapse or overdistension, potentially negating the benefits of VT reduction. EIT facilitates real-time monitoring of derecruitment associated with VT reduction, guiding physicians in determining the optimal PEEP value after each decrease in tidal volume. This original description of using EIT under ECCO2R to adjust PEEP at a level compromising between recruitability and overdistention could be a crucial element for future research on ECCO2R.

Air leak test in the Paediatric Intensive Care Unit (ALTIPICU): rationale and protocol for a prospective multicentre observational study.

INTRODUCTION: In children, respiratory distress due to upper airway obstruction (UAO) is a common complication of extubation. The quantitative cuff-leak test (qtCLT) is a simple, rapid and non-invasive test that has not been extensively studied in children. The objective of the ongoing study whose protocol is reported here is to investigate how well the qtCLT predicts UAO-related postextubation respiratory distress in paediatric intensive care unit (PICU) patients. METHODS AND ANALYSIS: Air Leak Test in the Paediatric Intensive Care Unit is a multicentre, prospective, observational study that will recruit 900 patients who are aged 2 days post-term to 17 years and ventilated through a cuffed endotracheal tube for at least 24 hours in any of 19 French PICUs. Within an hour of planned extubation, the qtCLT will be performed as a sequence of six measurements of the tidal volume with the cuff inflated then deflated. The primary outcome is the occurrence within 48 hours after extubation of severe UAO defined as combining a requirement for intravenous corticosteroid therapy and/or ventilator support by high-flow nasal cannula and/or by non-invasive ventilation or repeat invasive mechanical ventilation with a Westley score ≥4 with at least one point for stridor at each initiation. The results of the study are expected to identify risk factors for UAO-related postextubation respiratory distress and extubation failure, thereby identifying patient subgroups most likely to require preventive interventions. It will also determine whether qtCLT appears to be a reliable method to predict an increased risk for postextubation adverse events as severe UAO. ETHICS AND DISSEMINATION: The study was approved by the Robert Debré University Hospital institutional review board (IRB) on September 2021 (approval #2021578). The report of Robert Debré University Hospital IRB is valid for all sites, given the nature of the study with respect to the French law. The results will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT05328206.

Novel forms of ventilation in neonates: Neurally adjusted ventilatory assist and proportional assist ventilation.

Patient-triggered modes of ventilation are currently the standard of practice in the care of term and preterm infants. Maintaining spontaneous breathing during mechanical ventilation promotes earlier weaning and possibly reduces ventilator-induced diaphragmatic dysfunction. A further development of assisted ventilation provides support in proportion to the respiratory effort and enables the patient to have full control of their ventilatory cycle. In this paper we will review the literature on two of these modes of ventilation: neurally adjusted ventilatory assist (NAVA) and proportional assist ventilation (PAV), propose future studies and suggest clinical applications of these modes.