Diaphragm-protective Ventilation Research Articles

How to protect the diaphragm and the lung with diaphragm neurostimulation.

In the current review, we aim to highlight the evolving evidence on using diaphragm neurostimulation to develop lung and diaphragm protective mechanical ventilation. Positive-pressure ventilation (PPV) causes stress and strain to the lungs which leads to ventilator-induced lung injury (VILI). In addition, PPV is frequently associated with sedatives that induce excessive diaphragm unloading which contributes to ventilator-induced diaphragmatic dysfunction (VIDD). The nonvolitional diaphragmatic contractions entrained by diaphragm neurostimulation generate negative pressure ventilation, which may be a beneficial alternative or complement to PPV. Although well established as a permanent treatment of central apnea syndromes, temporary diaphragm neurostimulation rapidly evolves to prevent and treat VILI and VIDD. Experimental and small clinical studies report comprehensive data showing that diaphragm neurostimulation has the potential to mitigate VIDD and to decrease the stress and strain applied to the lungs. Scientific interest in temporary diaphragm neurostimulation has dramatically evolved in the last few years. Despite a solid physiological rationale and promising preliminary findings confirming a beneficial effect on the diaphragm and lungs, more studies and further technological advances will be needed to establish optimal standardized settings and lead to clinical implementation and improved outcomes.

Advances in achieving lung and diaphragm-protective ventilation.

Mechanical ventilation may have adverse effects on diaphragm and lung function. Lung- and diaphragm-protective ventilation is an approach that challenges the clinician to facilitate physiological respiratory efforts, while maintaining minimal lung stress and strain. Here, we discuss the latest advances in monitoring and interventions to achieve lung- and diaphragm protective ventilation. Noninvasive ventilator maneuvers (P0.1, airway occlusion pressure, pressure-muscle index) can accurately detect low and excessive respiratory efforts and high lung stress. Additional monitoring techniques include esophageal manometry, ultrasound, electrical activity of the diaphragm, and electrical impedance tomography. Recent trials demonstrate that a systematic approach to titrating inspiratory support and sedation facilitates lung- and diaphragm protective ventilation. Titration of positive-end expiratory pressure and, if available, veno-venous extracorporeal membrane oxygenation sweep gas flow may further modulate neural respiratory drive and effort to facilitate lung- and diaphragm protective ventilation. Achieving lung- and diaphragm-protective ventilation may require more than a single intervention; it demands a comprehensive understanding of the (neuro)physiology of breathing and mechanical ventilation, along with the application of a series of interventions under close monitoring. We suggest a bedside-approach to achieve lung- and diaphragm protective ventilation targets.

Transvenous phrenic nerve stimulation reduces diaphragm injury during controlled mechanical ventilation in a preclinical model of ARDS.

Patients with acute respiratory distress syndrome (ARDS) require periods of deep sedation and mechanical ventilation, leading to diaphragm dysfunction. Our study seeks to determine whether the combination of temporary transvenous diaphragm neurostimulation (TTDN) and mechanical ventilation changes the degree of diaphragm injury and cytokines concentration in a preclinical ARDS model. Moderate ARDS was induced in pigs using oleic acid, followed by ventilation for 12 h post-injury with volume-control at 8 mL/kg, positive end-expiratory pressure (PEEP) 5 cmH2O, respiratory rate and [Formula: see text] set to achieve normal arterial blood gases. Two groups received TTDN: every second breath (MV + TTDN50%, n = 6) or every breath (MV + TTDN100%, n = 6). One group received ventilation only (MV, n = 6). Full-thickness diaphragm and quadricep muscle biopsies were taken at study end. Samples were fixed and stained with hematoxylin and eosin and a point-counting technique was applied to calculate abnormal muscle area fraction. Cytokine concentrations were measured in homogenized tissue using porcine-specific enzyme-linked immunosorbent assay (ELISA) and compared with serum samples. Percentage of abnormal diaphragm tissue was different between MV [8.1% (6.0-8.8)] versus MV + TTDN50% [3.4% (2.1-4.8)], P = 0.010 and MV versus MV + TTDN100% [3.1% (2.5-4.0)], P = 0.005. Percentage of abnormal quadriceps tissue was not different between groups. Cytokine concentration patterns in diaphragm samples were different between all groups (P < 0.001) and the interaction between TTDN application and resultant cytokine concentration pattern was significant (P = 0.025). TTDN, delivered in synchrony with mechanical ventilation, mitigated diaphragm injury, as evidenced by less abnormal tissue in the diaphragm samples, in pigs with oleic acid-induced ARDS and is an exciting tool for lung and diaphragm-protective ventilation.NEW & NOTEWORTHY This study adds to our understanding of applying transvenous diaphragm neurostimulation synchronously with mechanical ventilation by examining its effects on diaphragm muscle injury and cytokine concentration patterns in pigs with acute respiratory distress syndrome (ARDS). We observed that using this therapy for 12 h post lung injury mitigated ventilator-induced diaphragm injury and changed the pattern of cytokine concentration measured in diaphragm tissue. These findings suggest that transvenous diaphragm neurostimulation is an exciting tool for lung and diaphragm protective ventilation.

Does patient-ventilator asynchrony really matter?

Past observational studies have reported the association between patient-ventilator asynchronies and poor clinical outcomes, namely longer duration of mechanical ventilation and higher mortality. But causality has remained undetermined. During the era of lung and diaphragm protective ventilation, should we revolutionize our clinical practice to detect and treat dyssynchrony? Clinicians' ability to recognize asynchronies is typically low. Automatized softwares based on artificial intelligence have been trained to largely outperform human eyesight and are close to be implemented at the bedside. There is growing evidence that in susceptible patients, dyssynchrony may lead to ventilation-induced lung injury (or patient self-inflicted lung injury) and that clusters of such dyssynchronous events have the highest association with poor outcomes. Dyssynchrony may also be associated with harm indirectly when it reflects over-assistance or over-sedation. However, the occurrence of reverse triggering by means of low inspiratory efforts during passive ventilation may prevent diaphragm dysfunction and atrophy and be beneficial. Most recent evidence on the topic suggests that synchrony between the patient and the mechanical ventilator is a critical element for protecting lung and diaphragm during the time of invasive mechanical ventilation or may reflect inadequate settings or sedation. Therefore, it is a complex situation, and clinical trials are still needed to test the effectiveness of keeping patient-ventilator interaction synchronous on clinical outcomes.

Phenotypes based on respiratory drive and effort to identify the risk factors when P0.1 fails to estimate ∆PES in ventilated children.

Monitoring respiratory effort and drive during mechanical ventilation is needed to deliver lung and diaphragm protection. Esophageal pressure (∆PES) is the gold standard measure of respiratory effort but is not routinely available. Airway occlusion pressure in the first 100ms of the breath (P0.1) is a readily available surrogate for both respiratory effort and drive but is only modestly correlated with ∆PES in children. We sought to identify risk factors for P0.1 over or underestimating ∆PES in ventilated children. Secondary analysis of physiological data from children and young adults enrolled in a randomized controlled trial testing lung and diaphragm protective ventilation in pediatric acute respiratory distress syndrome (PARDS) (NCT03266016). ∆PES (∆PES-REAL), P0.1 and predicted ∆PES (∆PES-PRED = 5.91*P0.1) were measured daily to identify phenotypes based upon the level of respiratory effort and drive: one passive (no spontaneous breathing), three where ∆PES-REAL and ∆PES-PRED were aligned (low, normal, and high effort and drive), two where ∆PES-REAL and ∆PES-PRED were mismatched (high underestimated effort, and overestimated effort). Logistic regression models were used to identify factors associated with each mismatch phenotype (High underestimated effort, or overestimated effort) as compared to all other spontaneous breathing phenotypes. We analyzed 953 patient days (222 patients). ∆PES-REAL and ∆PES-PRED were aligned in 536 (77%) of the active patient days. High underestimated effort (n = 119 (12%)) was associated with higher airway resistance (adjusted OR 5.62 (95%CI 2.58, 12.26) per log unit increase, p < 0.001), higher tidal volume (adjusted OR 1.53 (95%CI 1.04, 2.24) per cubic unit increase, p = 0.03), higher opioid use (adjusted OR 2.4 (95%CI 1.12, 5.13, p = 0.024), and lower set ventilator rate (adjusted OR 0.96 (95%CI 0.93, 0.99), p = 0.005). Overestimated effort was rare (n = 37 (4%)) and associated with higher alveolar dead space (adjusted OR 1.05 (95%CI 1.01, 1.09), p = 0.007) and lower respiratory resistance (adjusted OR 0.32 (95%CI 0.13, 0.81), p = 0.017). In patients with PARDS, P0.1 commonly underestimated high respiratory effort particularly with high airway resistance, high tidal volume, and high doses of opioids. Future studies are needed to investigate the impact of measures of respiratory effort, drive, and the presence of a mismatch phenotype on clinical outcome. NCT03266016; August 23, 2017.

Sedation-Ventilation Interaction in Acute Hypoxemic Respiratory Failure: Secondary Analysis of the Land and Diaphragm-Protective Ventilation by Means of Assessing Respiratory Work (LANDMARK) Trial

BackgroundVentilation and sedation are used for the management of acute hypoxemic respiratory failure (AHRF), but their optimal combination to minimize the risks of ventilation is not well understood. Research questionWhat are the individual effects and interactions of inspiratory and end-expiratory pressure (PEEP), sedation, and venovenous extracorporeal membrane oxygenation (VV-ECMO) on respiratory drive, effort, and lung-distending pressure in patients with AHRF triggering the ventilator? Study designand methods: Secondary exploratory analysis of a trial of lung and diaphragm protection in AHRF. Inspiratory pressure, sedation, PEEP, and VV-ECMO were titrated while respiratory drive (airway pressure in the first 100 milliseconds, P0.1), effort (esophageal pressure swing, |ΔPes|), and lung-distending pressure (dynamic transpulmonary driving pressure, ΔPL,dyn) were recorded. Associations were evaluated using linear mixed effects regression models including pre-specified terms for potential interactions. ResultsThe study included 223 individual measurements of P0.1 and 235 individual measurements of |ΔPes| and ΔPL,dyn from 30 patients. Propofol attenuated P0.1 (–0.4 cm H2O, 95% CI –0.3, –0.1 per 10 mcg/kg/min increase), |ΔPes| (–2.5 cm H2O, 95% CI –3.4, –1.7 per 10 mcg/kg/min increase) and ΔPL,dyn (–1.6 cm H2O, 95% CI –2.3, –0.8 per 10 mcg/kg/min increase). The effect of inspiratory pressure on |ΔPes| varied depending on propofol dose: with higher propofol dose, inspiratory pressure resulted in higher ΔPL,dyn. Under VV-ECMO, patients (n=16) had significantly lower |ΔPes| (–10 cm H2O, 95% CI –17.5, –2.5) and required less sedation to reduce |ΔPes| than without VV-ECMO (n=14). InterpretationMechanical ventilation, sedation, and VV-ECMO exert interdependent effects on respiratory drive, effort, and lung-distending pressure in AHRF. Patients under VV-ECMO require less sedation to control respiratory effort.

Lung- and diaphragm-protective strategies in acute respiratory failure: an in silico trial

BackgroundLung- and diaphragm-protective (LDP) ventilation may prevent diaphragm atrophy and patient self-inflicted lung injury in acute respiratory failure, but feasibility is uncertain. The objectives of this study were to estimate the proportion of patients achieving LDP targets in different modes of ventilation, and to identify predictors of need for extracorporeal carbon dioxide removal (ECCO2R) to achieve LDP targets.MethodsAn in silico clinical trial was conducted using a previously published mathematical model of patient–ventilator interaction in a simulated patient population (n = 5000) with clinically relevant physiological characteristics. Ventilation and sedation were titrated according to a pre-defined algorithm in pressure support ventilation (PSV) and proportional assist ventilation (PAV+) modes, with or without adjunctive ECCO2R, and using ECCO2R alone (without ventilation or sedation). Random forest modelling was employed to identify patient-level factors associated with achieving targets.ResultsAfter titration, the proportion of patients achieving targets was lower in PAV+ vs. PSV (37% vs. 43%, odds ratio 0.78, 95% CI 0.73–0.85). Adjunctive ECCO2R substantially increased the probability of achieving targets in both PSV and PAV+ (85% vs. 84%). ECCO2R alone without ventilation or sedation achieved LDP targets in 9%. The main determinants of success without ECCO2R were lung compliance, ventilatory ratio, and strong ion difference. In silico trial results corresponded closely with the results obtained in a clinical trial of the LDP titration algorithm (n = 30).ConclusionsIn this in silico trial, many patients required ECCO2R in combination with mechanical ventilation and sedation to achieve LDP targets. ECCO2R increased the probability of achieving LDP targets in patients with intermediate degrees of derangement in elastance and ventilatory ratio.

Mechanical Ventilation, Past, Present, and Future.

Mechanical ventilation (MV) has played a crucial role in the medical field, particularly in anesthesia and in critical care medicine (CCM) settings. MV has evolved significantly since its inception over 70 years ago and the future promises even more advanced technology. In the past, ventilation was provided manually, intermittently, and it was primarily used for resuscitation or as a last resort for patients with severe respiratory or cardiovascular failure. The earliest MV machines for prolonged ventilatory support and oxygenation were large and cumbersome. They required a significant amount of skills and expertise to operate. These early devices had limited capabilities, battery, power, safety features, alarms, and therefore these often caused harm to patients. Moreover, the physiology of MV was modified when mechanical ventilators moved from negative pressure to positive pressure mechanisms. Monitoring systems were also very limited and therefore the risks related to MV support were difficult to quantify, predict and timely detect for individual patients who were necessarily young with few comorbidities. Technology and devices designed to use tracheostomies versus endotracheal intubation evolved in the last century too and these are currently much more reliable. In the present, positive pressure MV is more sophisticated and widely used for extensive period of time. Modern ventilators use mostly positive pressure systems and are much smaller, more portable than their predecessors, and they are much easier to operate. They can also be programmed to provide different levels of support based on evolving physiological concepts allowing lung-protective ventilation. Monitoring systems are more sophisticated and knowledge related to the physiology of MV is improved. Patients are also more complex and elderly compared to the past. MV experts are informed about risks related to prolonged or aggressive ventilation modalities and settings. One of the most significant advances in MV has been protective lung ventilation, diaphragm protective ventilation including noninvasive ventilation (NIV). Health care professionals are familiar with the use of MV and in many countries, respiratory therapists have been trained for the exclusive purpose of providing safe and professional respiratory support to critically ill patients. Analgo-sedation drugs and techniques are improved, and more sedative drugs are available and this has an impact on recovery, weaning, and overall patients' outcome. Looking toward the future, MV is likely to continue to evolve and improve alongside monitoring techniques and sedatives. There is increasing precision in monitoring global "patient-ventilator" interactions: structure and analysis (asynchrony, desynchrony, etc). One area of development is the use of artificial intelligence (AI) in ventilator technology. AI can be used to monitor patients in real-time, and it can predict when a patient is likely to experience respiratory distress. This allows medical professionals to intervene before a crisis occurs, improving patient outcomes and reducing the need for emergency intervention. This specific area of development is intended as "personalized ventilation." It involves tailoring the ventilator settings to the individual patient, based on their physiology and the specific condition they are being treated for. This approach has the potential to improve patient outcomes by optimizing ventilation and reducing the risk of harm. In conclusion, MV has come a long way since its inception, and it continues to play a critical role in anesthesia and in CCM settings. Advances in technology have made MV safer, more effective, affordable, and more widely available. As technology continues to improve, more advanced and personalized MV will become available, leading to better patients' outcomes and quality of life for those in need.

Non-invasive patient breathing effort identification: a b-spline and mixed integer solution

Accurate identification of patient breathing efforts is imperative to the delivery of lung and diaphragm protective ventilation. Existing model-based approaches constrain the allowable shape of the patient effort pressure-time profile to improve model identifiability. A novel method – coined the B-MIQP technique – is presented that extends upon existing methods with aims to further improve identification accuracy. B-spline basis functions and binary decision variables are utilised within a single compartment framework to describe the patient effort pressure-time profile. With reference to the experimental results, identified elastance and resistance values were within expected ranges, while identified patient effort outcomes matched physiological expectations and reflected trends when compared to esophageal pressure signals.

Estimation of inspiratory effort using airway occlusion maneuvers in ventilated children: a secondary analysis of an ongoing randomized trial testing a lung and diaphragm protective ventilation strategy

BackgroundMonitoring respiratory effort in ventilated patients is important to balance lung and diaphragm protection. Esophageal manometry remains the gold standard for monitoring respiratory effort but is invasive and requires expertise for its measurement and interpretation. Airway pressures during occlusion maneuvers may provide an alternative, although pediatric data are limited. We sought to determine the correlation between change in esophageal pressure during tidal breathing (∆Pes) and airway pressure measured during three airway occlusion maneuvers: (1) expiratory occlusion pressure (Pocc), (2) airway occlusion pressure (P0.1), and (3) respiratory muscle pressure index (PMI) in children. We also sought to explore pediatric threshold values for these pressures to detect excessive or insufficient respiratory effort.MethodsSecondary analysis of physiologic data from children between 1 month and 18 years of age with acute respiratory distress syndrome enrolled in an ongoing randomized clinical trial testing a lung and diaphragm protective ventilation strategy (REDvent, R01HL124666). ∆Pes, Pocc, P0.1, and PMI were measured. Repeated measure correlations were used to investigate correlation coefficients between ∆Pes and the three measures, and linear regression equations were generated to identify potential therapeutic thresholds.ResultsThere were 653 inspiratory and 713 expiratory holds from 97 patients. Pocc had the strongest correlation with ∆Pes (r = 0.68), followed by PMI (r = 0.60) and P0.1 (r = 0.42). ∆Pes could be reliably estimated using the regression equation ∆Pes = 0.66 times Pocc (R2 = 0.82), with Pocc cut-points having high specificity and moderate sensitivity to detect respective ∆Pes thresholds for high and low respiratory effort. There were minimal differences in the relationship between Pocc and ∆Pes based on age (infant, child, adolescent) or mode of ventilation (SIMV versus Pressure Support), although these differences were more apparent with P0.1 and PMI.ConclusionsAirway occlusion maneuvers may be appropriate alternatives to esophageal pressure measurement to estimate the inspiratory effort in children, and Pocc represents the most promising target.Trial registration: NCT03266016; August 23, 2017.

Computational physiological models for individualised mechanical ventilation: a systematic literature review focussing on quality, availability, and clinical readiness

BackgroundIndividualised optimisation of mechanical ventilation (MV) remains cumbersome in modern intensive care medicine. Computerised, model-based support systems could help in tailoring MV settings to the complex interactions between MV and the individual patient's pathophysiology. Therefore, we critically appraised the current literature on computational physiological models (CPMs) for individualised MV in the ICU with a focus on quality, availability, and clinical readiness.MethodsA systematic literature search was conducted on 13 February 2023 in MEDLINE ALL, Embase, Scopus and Web of Science to identify original research articles describing CPMs for individualised MV in the ICU. The modelled physiological phenomena, clinical applications, and level of readiness were extracted. The quality of model design reporting and validation was assessed based on American Society of Mechanical Engineers (ASME) standards.ResultsOut of 6,333 unique publications, 149 publications were included. CPMs emerged since the 1970s with increasing levels of readiness. A total of 131 articles (88%) modelled lung mechanics, mainly for lung-protective ventilation. Gas exchange (n = 38, 26%) and gas homeostasis (n = 36, 24%) models had mainly applications in controlling oxygenation and ventilation. Respiratory muscle function models for diaphragm-protective ventilation emerged recently (n = 3, 2%). Three randomised controlled trials were initiated, applying the Beacon and CURE Soft models for gas exchange and PEEP optimisation. Overall, model design and quality were reported unsatisfactory in 93% and 21% of the articles, respectively.ConclusionCPMs are advancing towards clinical application as an explainable tool to optimise individualised MV. To promote clinical application, dedicated standards for quality assessment and model reporting are essential.Trial registration number PROSPERO—CRD42022301715. Registered 05 February, 2022.

Monitoring Respiratory Effort and Lung-distending Pressure Noninvasively during Mechanical Ventilation: Ready for Prime Time.

Monitoring Respiratory Effort and Lung-distending Pressure Noninvasively during Mechanical Ventilation: Ready for Prime Time.

Diaphragm-Protective Mechanical Ventilation: Saving the Diaphragm from the Detrimental Effects of Mechanical Ventilation

Diaphragm weakness develops in up to 80% of the critically ill patients, and is associated with adverse clinical outcomes. Mechanical ventilation has been proposed to play a role in the development of diaphragm weakness in critically ill patients, especially by ventilator under-assist or ventilator over-assist. Therefore, in addition to the concept of lung-protective ventilation to protect the lung, diaphragm-protective ventilation has been recently proposed to limit the development of diaphragm weakness. In this concise review, we will discuss the current evidence for diaphragm-protective ventilation and the clinical consequences.

Strategies for lung- and diaphragm-protective ventilation in acute hypoxemic respiratory failure: a physiological trial

BackgroundInsufficient or excessive respiratory effort during acute hypoxemic respiratory failure (AHRF) increases the risk of lung and diaphragm injury. We sought to establish whether respiratory effort can be optimized to achieve lung- and diaphragm-protective (LDP) targets (esophageal pressure swing − 3 to − 8 cm H2O; dynamic transpulmonary driving pressure ≤ 15 cm H2O) during AHRF.MethodsIn patients with early AHRF, spontaneous breathing was initiated as soon as passive ventilation was not deemed mandatory. Inspiratory pressure, sedation, positive end-expiratory pressure (PEEP), and sweep gas flow (in patients receiving veno-venous extracorporeal membrane oxygenation (VV-ECMO)) were systematically titrated to achieve LDP targets. Additionally, partial neuromuscular blockade (pNMBA) was administered in patients with refractory excessive respiratory effort.ResultsOf 30 patients enrolled, most had severe AHRF; 16 required VV-ECMO. Respiratory effort was absent in all at enrolment. After initiating spontaneous breathing, most exhibited high respiratory effort and only 6/30 met LDP targets. After titrating ventilation, sedation, and sweep gas flow, LDP targets were achieved in 20/30. LDP targets were more likely to be achieved in patients on VV-ECMO (median OR 10, 95% CrI 2, 81) and at the PEEP level associated with improved dynamic compliance (median OR 33, 95% CrI 5, 898). Administration of pNMBA to patients with refractory excessive effort was well-tolerated and effectively achieved LDP targets.ConclusionRespiratory effort is frequently absent under deep sedation but becomes excessive when spontaneous breathing is permitted in patients with moderate or severe AHRF. Systematically titrating ventilation and sedation can optimize respiratory effort for lung and diaphragm protection in most patients. VV-ECMO can greatly facilitate the delivery of a LDP strategy.Trial registration: This trial was registered in Clinicaltrials.gov in August 2018 (NCT03612583).

Lung and diaphragm protective ventilation: a synthesis of recent data

ABSTRACT Introduction : To adhere to the Hippocratic Oath, to ‘first, do no harm’, we need to make every effort to minimize the adverse effects of mechanical ventilation. Our understanding of the mechanisms of ventilator-induced lung injury (VILI) and ventilator-induced diaphragm dysfunction (VIDD) has increased in recent years. Research focuses now on methods to monitor lung stress and inhomogeneity and targets we should aim for when setting the ventilator. In parallel, efforts to promote early assisted ventilation to prevent VIDD have revealed new challenges, such as titrating inspiratory effort and synchronizing the mechanical with the patients’ spontaneous breaths, while at the same time adhering to lung-protective targets. Areas covered This is a narrative review of the key mechanisms contributing to VILI and VIDD and the methods currently available to evaluate and mitigate the risk of lung and diaphragm injury. Expert opinion Implementing lung and diaphragm protective ventilation requires individualizing the ventilator settings, and this can only be accomplished by exploiting in everyday clinical practice the tools available to monitor lung stress and inhomogeneity, inspiratory effort, and patient–ventilator interaction.

Lung- and Diaphragm-Protective Ventilation by Titrating Inspiratory Support to Diaphragm Effort: A Randomized Clinical Trial.

Lung- and diaphragm-protective ventilation is a novel concept that aims to limit the detrimental effects of mechanical ventilation on the diaphragm while remaining within limits of lung-protective ventilation. The premise is that low breathing effort under mechanical ventilation causes diaphragm atrophy, whereas excessive breathing effort induces diaphragm and lung injury. In a proof-of-concept study, we aimed to assess whether titration of inspiratory support based on diaphragm effort increases the time that patients have effort in a predefined "diaphragm-protective" range, without compromising lung-protective ventilation. Randomized clinical trial. Mixed medical-surgical ICU in a tertiary academic hospital in the Netherlands. Patients (n = 40) with respiratory failure ventilated in a partially-supported mode. In the intervention group, inspiratory support was titrated hourly to obtain transdiaphragmatic pressure swings in the predefined "diaphragm-protective" range (3-12 cm H2O). The control group received standard-of-care. Transdiaphragmatic pressure, transpulmonary pressure, and tidal volume were monitored continuously for 24 hours in both groups. In the intervention group, more breaths were within "diaphragm-protective" range compared with the control group (median 81%; interquartile range [64-86%] vs 35% [16-60%], respectively; p < 0.001). Dynamic transpulmonary pressures (20.5 ± 7.1 vs 18.5 ± 7.0 cm H2O; p = 0.321) and tidal volumes (7.56 ± 1.47 vs 7.54 ± 1.22 mL/kg; p = 0.961) were not different in the intervention and control group, respectively. Titration of inspiratory support based on patient breathing effort greatly increased the time that patients had diaphragm effort in the predefined "diaphragm-protective" range without compromising tidal volumes and transpulmonary pressures. This study provides a strong rationale for further studies powered on patient-centered outcomes.

Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock 2021, interpretation and expectation

The Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock 2021 (2021 guidelines) was recently released. The guidelines summarized the evidences from literatures up to July 2019, and composed by 6 parts as "screening and early treatment", "infection", "hemodynamic management", "ventilation", "additional therapies" and "long-term outcomes and goals of care" with a total of 93 items and 99 recommendations. Compared with the 2016 guidelines (96 recommendations), although the total number of recommendations in the 2021 guidelines is similar, the number of "strong recommendations (recommend)" in 2021 guidelines has dropped significantly, as the number of "weak recommendations (suggest)" has increased significantly, and the level of the quality of evidence on which the recommendations are based has been significantly lowered. Furthermore, 2021 guidelines have also markedly deleted or simplified the recommendations regarding infection prevention, acute respiratory distress syndrome (ARDS) treatment, nutritional support and so on. While, the most obvious improvement appears in the segment of "long-term outcomes and goals of care", in which the patients and their families could get help in term of determining their physical rehabilitation and discharge follow-up plans and formulating exact goals of care. 2021 guidelines did not adopt new and emerging therapies or treatments, such as metagenomic next-generation sequencing (mNGS), diaphragm protective ventilation, timing of initiating renal replacement therapy for acute kidney injury, early mobility, endotoxin adsorption, tranexamic acid, E-medicine and telemedicine, big data and artificial intelligence and other new therapies. Collectively, it may suggest the 2021 guidelines tend to be conservative and simplified rather than fairly optimized and logicalized, which may arouse controversy in the future and affect clinician compliance.

Диафрагм-протективная искусственная вентиляция легких на этапе отлучения от респираторной терапии у детей

Актуальность. Искусственная вентиляция легких (ИВЛ) у значительной части пациентов может вызывать диафрагмальную дисфункцию, которую связывают с неблагоприятными результатами лечения, длительным отлучением от респираторной терапии и длительным пребыванием в отделении интенсивной терапии. Целью исследования было установить эффективность диафрагм-протективной стратегии в дополнение к легочно-протективной стратегии при проведении отлучения от ИВЛ у детей. Рабочей была гипотеза, что проведение диафрагм-протективной и легочно-протективной стратегий ИВЛ не будет влиять на уровень дис­пноэ, продолжительность отлучения от ИВЛ, длительность пребывания в отделении интенсивной терапии. Материалы и методы. Нами проведено проспективное когортное одноцентровое исследование в отделении анестезиологии с койками интенсивной терапии КНП «Львовская областная детская клиническая больница «ОХМАТДЕТ». В исследование было включено 89 пациентов в возрасте от 1 мес. до 18 лет. Все пациенты было разделены случайным образом на 2 группы (с помощью сервиса random.org). В I группу вошли пациенты, у которых применяли легочно-протективную стратегию ИВЛ, во II группу — пациенты, у которых применяли легочно-протективную и диафрагм-протективную стратегии ИВЛ. В анализ данных включены 82 пациента. Мы изучали показатели функции диафрагмы (фракцию ее истончения и амплитуду движений), показатели кислотно-щелочного равновесия крови. Нами были проанализированы уровень диспноэ по шкале D-VAS для пациентов 6–18 лет, частота успешного отлучения от ИВЛ (отсутствие необходимости проводить ИВЛ в течение более 48 часов с момента экстубации пациента и прекращение механической поддержки его дыхания), а также длительность проведения ИВЛ и длительность госпитализации в отделении интенсивной терапии. Результаты. В нашем исследовании установлено, что в І группе были успешно отлучены от ИВЛ 72,1 % пациентов, тогда как во II группе — 86,8 % (p = 0,05). Продолжительность проведения ИВЛ была большей во II группе пациентов по сравнению с I группой и составила 19,4 ± 2,6 и 23,1 ± 2,2 дня соответственно (p = 0,12). Такое увеличение продолжительности ИВЛ у пациентов II группы следует интерпретировать вместе с показателем успешности отлучения от ИВЛ, который был выше в данной группе больных. Можно предположить, что большую клиническую ценность для пациента имел факт успешного отлучения, чем собственно длительность ИВЛ, однако такая трактовка результатов исследования требует дальнейшего изучения. Продолжительность госпитализации в отделении интенсивной терапии была выше среди пациентов I группы по сравнению со II группой и составила 29,2 ± 3,1 и 26,5 ± 3,6 дня соответственно (p = 0,06). Выводы. Комплексный подход на этапе отлучения от ИВЛ, включая проведение диафрагм-протективной стратегии в дополнение к легочно-протективной, позволяет уменьшить частоту диспноэ у пациентов, повысить вероятность успешного отлучения от искусственной вентиляции легких и сократить время пребывания пациента в отделении интенсивной терапии.

Diaphragm neurostimulation during mechanical ventilation reduces atelectasis and transpulmonary plateau pressure, preserving lung homogeneity and [Formula: see text]/[Formula: see text

Tidal volume delivered by mechanical ventilation to a sedated patient is distributed in a nonphysiological pattern, causing atelectasis (underinflation) and overdistension (overinflation). Activation of the diaphragm during controlled mechanical ventilation in these sedated patients may provide a method to reduce atelectasis and alveolar inhomogeneity, protecting the lungs from ventilator-induced lung injury while also protecting the diaphragm by preventing ventilator-induced diaphragm dysfunction. We studied the hypothesis that diaphragm contractions elicited by transvenous phrenic nerve stimulation, delivered in synchrony with volume-control ventilation, would reduce atelectasis and lung inhomogeneity in a healthy, normal lung pig model. Twenty-five large pigs were ventilated for 50 h with lung-protective volume-control ventilation combined with synchronous transvenous phrenic-nerve neurostimulation on every breath, or every second breath. This was compared to lung-protective ventilation alone. Lung mechanics and ventilation pressures were measured using esophageal pressure manometry and electrical impedance tomography. Alveolar homogeneity was measured using alveolar chord length of preserved lung tissue. Lung injury was measured using inflammatory cytokine concentration in bronchoalveolar lavage fluid and serum. We found that diaphragm neurostimulation on every breath preserved [Formula: see text]/[Formula: see text] and significantly reduced the loss of end-expiratory lung volume after 50 h of mechanical ventilation. Neurostimulation on every breath reduced plateau and driving pressures, improved both static and dynamic compliance and resulted in less alveolar inhomogeneity. These findings support that temporary transvenous diaphragm neurostimulation during volume-controlled, lung-protective ventilation may offer a potential method to provide both lung- and diaphragm-protective ventilation.NEW & NOTEWORTHY Temporary transvenous diaphragm neurostimulation has been shown to mitigate diaphragm atrophy in a preclinical model. This study contributes to this work by demonstrating that diaphragm neurostimulation can also offer lung protection from ventilator injury, providing a potential solution to the dilemma of lung- versus diaphragm-protective ventilation. Our findings show that neurostimulation on every breath preserved [Formula: see text]/[Formula: see text], end-expiratory lung volume, alveolar homogeneity, and required lower pressures than lung-protective ventilation over 50 h in healthy pigs.

Non-invasive method to detect high respiratory effort and transpulmonary driving pressures in COVID-19 patients during mechanical ventilation

BackgroundHigh respiratory drive in mechanically ventilated patients with spontaneous breathing effort may cause excessive lung stress and strain and muscle loading. Therefore, it is important to have a reliable estimate of respiratory effort to guarantee lung and diaphragm protective mechanical ventilation. Recently, a novel non-invasive method was found to detect excessive dynamic transpulmonary driving pressure (∆PL) and respiratory muscle pressure (Pmus) with reasonable accuracy. During the Coronavirus disease 2019 (COVID-19) pandemic, it was impossible to obtain the gold standard for respiratory effort, esophageal manometry, in every patient. Therefore, we investigated whether this novel non-invasive method could also be applied in COVID-19 patients.Methods∆PL and Pmus were derived from esophageal manometry in COVID-19 patients. In addition, ∆PL and Pmus were computed from the occlusion pressure (∆Pocc) obtained during an expiratory occlusion maneuver. Measured and computed ∆PL and Pmus were compared and discriminative performance for excessive ∆PL and Pmus was assessed. The relation between occlusion pressure and respiratory effort was also assessed.ResultsThirteen patients were included. Patients had a low dynamic lung compliance [24 (20–31) mL/cmH2O], high ∆PL (25 ± 6 cmH2O) and high Pmus (16 ± 7 cmH2O). Low agreement was found between measured and computed ∆PL and Pmus. Excessive ∆PL > 20 cmH2O and Pmus > 15 cmH2O were accurately detected (area under the receiver operating curve (AUROC) 1.00 [95% confidence interval (CI), 1.00–1.00], sensitivity 100% (95% CI, 72–100%) and specificity 100% (95% CI, 16–100%) and AUROC 0.98 (95% CI, 0.90–1.00), sensitivity 100% (95% CI, 54–100%) and specificity 86% (95% CI, 42–100%), respectively). Respiratory effort calculated per minute was highly correlated with ∆Pocc (for esophageal pressure time product per minute (PTPes/min) r2 = 0.73; P = 0.0002 and work of breathing (WOB) r2 = 0.85; P < 0.0001).Conclusions∆PL and Pmus can be computed from an expiratory occlusion maneuver and can predict excessive ∆PL and Pmus in patients with COVID-19 with high accuracy.