Physiologic Effects of Extracorporeal Membrane Oxygenation in Patients with Severe Acute Respiratory Distress Syndrome.

Rationale: Blood flow rate affects mixed venous oxygenation (SvO2) during venovenous extracorporeal membrane oxygenation (ECMO), with possible effects on the pulmonary circulation and the right heart function. Objectives: To describe the physiologic effects of different levels of SvO2 obtained by changing ECMO blood flow in patients with severe acute respiratory distress syndrome receiving ECMO and controlled mechanical ventilation. Methods: Low (SvO2 target, 70-75%), intermediate (SvO2 target, 75-80%), and high (SvO2 target, >80%) ECMO blood flows were applied for 30 minutes in random order in 20 patients. Mechanical ventilation settings were left unchanged. The hemodynamic and pulmonary effects were assessed with pulmonary artery catheter and electrical impedance tomography. Measurements and Main Results: Cardiac output decreased from low to intermediate and to high blood flow/SvO2 (9.2 [6.2-10.9] vs. 8.3 [5.9-9.8] vs. 7.9 [6.5-9.1] L/min; P = 0.014), as well as mean pulmonary artery pressure (34 ± 6 vs. 31 ± 6 vs. 30 ± 5 mm Hg; P < 0.001) and right ventricular stroke work index (14.2 ± 4.4 vs. 12.2 ± 3.6 vs. 11.4 ± 3.2 g × m/beat/m2; P = 0.002). Cardiac output was inversely correlated with mixed venous and arterial Po2 values (R2 = 0.257; P = 0.031; and R2 = 0.324; P = 0.05). Pulmonary artery pressure was correlated with decreasing mixed venous Po2 (R2 = 0.29; P < 0.001) and with increasing cardiac output (R2 = 0.378; P < 0.007). Measures of [Formula: see text]/[Formula: see text] mismatch did not differ between the three steps. Conclusions: In patients with severe acute respiratory distress syndrome, increased ECMO blood flow rate resulting in higher SvO2 decreases pulmonary artery pressure, cardiac output, and right heart workload.

Impact of Positive End-Expiratory Pressure and FiO2 on Lung Mechanics and Intrapulmonary Shunt in Mechanically Ventilated Patients with ARDS Due to COVID-19 Pneumonia.

Purpose: This study aimed to investigate the effects of inspired oxygen fraction (FiO2) and positive end-expiratory pressure (PEEP) on gas exchange in mechanically ventilated patients with COVID-19. Methods: Two FiO2 (100%, 40%) were tested at 3 decreasing levels of PEEP (15, 10, and 5 cmH2O). At each FiO2 and PEEP, gas exchange, respiratory mechanics, hemodynamics, and the distribution of ventilation and perfusion were assessed with electrical impedance tomography. The impact of FiO2 on the intrapulmonary shunt (delta shunt) was analyzed as the difference between the calculated shunt at FiO2 100% (shunt) and venous admixture at FiO2 40% (venous admixture). Results: Fourteen patients were studied. Decreasing PEEP from 15 to 10 cmH2O did not change shunt (24 [21-28] vs 27 [24-29]%) or venous admixture (18 [15-26] vs 23 [18-34]%) while partial pressure of arterial oxygen (FiO2 100%) was higher at PEEP 15 (262 [198-338] vs 256 [147-315] mmHg; P < .05). Instead when PEEP was decreased from 10 to 5 cmH2O, shunt increased to 36 [30-39]% (P < .05) and venous admixture increased to 33 [30-43]% (P < .05) and partial pressure of arterial oxygen (100%) decreased to 109 [76-177] mmHg (P < .05). At PEEP 15, administration of 100% FiO2 resulted in a shunt greater than venous admixture at 40% FiO2, ((24 [21-28] vs 18 [15-26]%, P = .005), delta shunt 5.5% (2.3-8.8)). Compared to PEEP 10, PEEP of 5 and 15 cmH2O resulted in decreased global and pixel-level compliance. Cardiac output at FiO2 100% resulted higher at PEEP 5 (5.4 [4.4-6.5]) compared to PEEP 10 (4.8 [4.1-5.5], P < .05) and PEEP 15 cmH2O (4.7 [4.5-5.4], P < .05). Conclusion: In this study, PEEP of 15 cmH2O, despite resulting in the highest oxygenation, was associated with overdistension. PEEP of 5 cmH2O was associated with increased shunt and alveolar collapse. Administration of 100% FiO2 was associated with an increase in intrapulmonary shunt in the setting of high PEEP. Trial registration: NCT05132933.

Right Ventricular Limitation: A Tale of Two Elastances.

Right ventricular (RV) dysfunction is a commonly considered cause of low cardiac output in critically ill patients. Its management can be difficult and requires an understanding of how the RV limits cardiac output. We explain that RV stroke output is caught between the passive elastance of the RV walls during diastolic filling and the active elastance produced by the RV in systole. These two elastances limit RV filling and stroke volume and consequently limit left ventricular stroke volume. We emphasize the use of the term "RV limitation" and argue that limitation of RV filling is the primary pathophysiological process by which the RV causes hemodynamic instability. Importantly, RV limitation can be present even when RV function is normal. We use the term "RV dysfunction" to indicate that RV end-systolic elastance is depressed or diastolic elastance is increased. When RV dysfunction is present, RV limitation occurs at lowerpulmonary valve opening pressures and lower stroke volume, but stroke volume and cardiac output still can be maintained until RV filling is limited. We use the term "RV failure" to indicate the condition in which RV output is insufficient for tissue needs. We discuss the physiological underpinnings of these terms and implications for clinical management.

Effects of an asymmetrical high flow nasal cannula interface in hypoxemic patients.

BACKGROUND: Optimal noninvasive respiratory support for patients with hypoxemic respiratory failure should minimize work of breathing without increasing the transpulmonary pressure. Recently, an asymmetrical high flow nasal cannula (HFNC) interface (Duet, Fisher & Paykel Healthcare Ltd), in which the caliber of each nasal prong is different, was approved for clinical use. This system might reduce work of breathing by lowering minute ventilation and improving respiratory mechanics. METHODS: We enrolled 10 patients ≥ 18 years of age who were admitted to the Ospedale Maggiore Policlinico ICU in Milan, Italy, and had a PaO2/FiO2 < 300 mmHg during HFNC support with a conventional cannula. We investigated whether the asymmetrical interface, compared to a conventional high flow nasal cannula, reduces minute ventilation and work of breathing. Each patient underwent support with the asymmetrical interface and the conventional interface, applied in a randomized sequence. Each interface was provided at a flow rate of 40 l/min followed by 60 l/min. Patients were continuously monitored with esophageal manometry and electrical impedance tomography. RESULTS: Application of the asymmetrical interface resulted in a -13.5 [-19.4 to (-4.5)] % change in minute ventilation at a flow rate of 40 l/min, p = 0.006 and a -19.6 [-28.0 to (-7.5)] % change at 60 l/min, p = 0.002, that occurred despite no change in PaCO2 (35 [33-42] versus 35 [33-43] mmHg at 40 l/min and 35 [32-41] versus 36 [32-43] mmHg at 60 l/min). Correspondingly, the asymmetrical interface lowered the inspiratory esophageal pressure-time product from 163 [118-210] to 140 [84-159] (cmH2O*s)/min at a flow rate of 40 l/min, p = 0.02 and from 142 [123-178] to 117 [90-137] (cmH2O*s)/min at a flow rate of 60 l/min, p = 0.04. The asymmetrical cannula did not have any impact on oxygenation, the dorsal fraction of ventilation, dynamic lung compliance, or end-expiratory lung impedance, suggesting no major effect on PEEP, lung mechanics, or alveolar recruitment. CONCLUSIONS: An asymmetrical HFNC interface reduces minute ventilation and work of breathing in patients with mild-to-moderate hypoxemic respiratory failure supported with a conventional interface. This appears to be primarily driven by increased ventilatory efficiency due to enhanced CO2 clearance from the upper airway.

Clinical risk factors for increased respiratory drive in intubated hypoxemic patients.

BACKGROUND: There is very limited evidence identifying factors that increase respiratory drive in hypoxemic intubated patients. Most physiological determinants of respiratory drive cannot be directly assessed at the bedside (e.g., neural inputs from chemo- or mechano-receptors), but clinical risk factors commonly measured in intubated patients could be correlated with increased drive. We aimed to identify clinical risk factors independently associated with increased respiratory drive in intubated hypoxemic patients. METHODS: We analyzed the physiological dataset from a multicenter trial on intubated hypoxemic patients on pressure support (PS). Patients with simultaneous assessment of the inspiratory drop in airway pressure at 0.1-s during an occlusion (P0.1) and risk factors for increased respiratory drive on day 1 were included. We evaluated the independent correlation of the following clinical risk factors for increased drive with P0.1: severity of lung injury (unilateral vs. bilateral pulmonary infiltrates, PaO2/FiO2, ventilatory ratio); arterial blood gases (PaO2, PaCO2 and pHa); sedation (RASS score and drug type); SOFA score; arterial lactate; ventilation settings (PEEP, level of PS, addition of sigh breaths). RESULTS: Two-hundred seventeen patients were included. Clinical risk factors independently correlated with higher P0.1 were bilateral infiltrates (increase ratio [IR] 1.233, 95%CI 1.047-1.451, p = 0.012); lower PaO2/FiO2 (IR 0.998, 95%CI 0.997-0.999, p = 0.004); higher ventilatory ratio (IR 1.538, 95%CI 1.267-1.867, p < 0.001); lower pHa (IR 0.104, 95%CI 0.024-0.464, p = 0.003). Higher PEEP was correlated with lower P0.1 (IR 0.951, 95%CI 0.921-0.982, p = 0.002), while sedation depth and drugs were not associated with P0.1. CONCLUSIONS: Independent clinical risk factors for higher respiratory drive in intubated hypoxemic patients include the extent of lung edema and of ventilation-perfusion mismatch, lower pHa, and lower PEEP, while sedation strategy does not affect drive. These data underline the multifactorial nature of increased respiratory drive.

Right Ventricular Loading by Lung Inflation during Controlled Mechanical Ventilation.

Rationale: The inspiratory rise in transpulmonary pressure during mechanical ventilation increases right ventricular (RV) afterload. One mechanism is that when Palv exceeds left atrial pressure, West zone 1 or 2 (non-zone 3) conditions develop, and Palv becomes the downstream pressure opposing RV ejection. The Vt at which this impact on the right ventricle becomes hemodynamically evident is not well established. Objectives: To determine the magnitude of RV afterload and prevalence of significant non-zone 3 conditions during inspiration across the range of Vt currently prescribed in clinical practice. Methods: In postoperative passively ventilated cardiac surgery patients, we measured right atrial, right ventricle, pulmonary artery, pulmonary artery occlusion pressure, plateau pressure, and esophageal pressure during short periods of controlled ventilation, with Vt increments ranging between 2 and 12 ml/kg predicted body weight (PBW). The inspiratory increase in RV afterload was evaluated hemodynamically and echocardiographically. The prevalence of non-zone 3 conditions was determined using two definitions based on changes in esophageal pressure, pulmonary artery occlusion pressure, and plateau pressure. Measurements and Main Results: Fifty-one patients were studied. There was a linear relationship between Vt, driving pressure, transpulmonary pressure, and the inspiratory increase in the RV isovolumetric contraction pressure. Echocardiographically, increasing Vt was associated with a greater inspiratory increase in markers of afterload and a decrease in stroke volume. Non-zone 3 conditions were present in >50% of subjects at a Vt ⩾ 6 ml/kg PBW. Conclusions: In the Vt range currently prescribed, RV afterload increases with increasing Vt. A mechanical ventilation strategy that limits Vt and driving pressure is cardioprotective.

Integrating electrical impedance tomography and transpulmonary pressure monitoring to personalize PEEP in hypoxemic patients undergoing pressure support ventilation.

Monitoring with electrical impedance tomography (EIT) during a decremental PEEP trial has been used to identify the PEEP that yields the optimal balance of pulmonary overdistension and collapse. This method is based on pixel-level changes in respiratory system compliance and depends on fixed or measured airway driving pressure. We developed a novel approach to quantify overdistension and collapse during pressure support ventilation (PSV) by integrating transpulmonary pressure and EIT monitoring and performed pilot tests in three hypoxemic patients. We report that our experimental approach is feasible and capable of identifying a PEEP that balances overdistension and collapse in intubated hypoxemic patients undergoing PSV.

Bioimpedance-measured volume overload predicts longer duration of mechanical ventilation in intensive care unit patients.

PURPOSE: Bioelectrical impedance analysis (BIA) is a technology that provides a rapid, non-invasive measurement of volume in body compartments and may aid the physician in the assessment of volume status. We sought to investigate the effect of BIA-measured volume status on duration of mechanical ventilation, 28-day mortality, and acute kidney injury requiring renal replacement therapy in a population of medical/surgical patients admitted to the intensive care unit (ICU). METHODS: Prospective observational study of adult patients who required mechanical ventilation within 24 hr of admission to ICU. Bioelectrical impedance analysis measured extracellular water (ECW) and total body water (TBW) and these measurements were recorded on days 1, 3, 5, and 7. RESULTS: A total of 36 patients were enrolled. Mean (standard deviation) age was 61.8 (21.3) years and 31% of patients were female. The majority were admitted from the emergency department or operating room. The most common diagnosis was sepsis. At 28 days, eight patients (22%) had died. There was no association between ECW/TBW ratio at day 1 and 28-day mortality (odds ratio, 1.2; 95% confidence interval [CI], 0.6 to 2.3) after adjusting for age, sex, and Acute Physiology and Chronic Health Evaluation II score. The median [interquartile range] number of ventilator days was 5 [2.5-7.5]. On day 1, for each 1% increase in the ECW/TBW ratio, there was a 1.2-fold increase in ventilator days (95% CI, 1.003 to 1.4; P = 0.05). It is notable that 20% of eligible patients could not be enrolled because medical equipment interfered with correct electrode placement. CONCLUSION: Bioimpedance-measured ECW/TBW on day 1 of admission to the ICU is associated with time on the ventilator. While this technology may be a useful adjunct to the clinical assessment of volume status, there are technical barriers to its routine use in a general ICU population.

Clinical and Experimental Evidence for Patient Self-Inflicted Lung Injury (P-SILI) and Bedside Monitoring.

Patient self-inflicted lung injury (P-SILI) is a major challenge for the ICU physician: although spontaneous breathing is associated with physiological benefits, in patients with acute respiratory distress syndrome (ARDS), the risk of uncontrolled inspiratory effort leading to additional injury needs to be assessed to avoid delayed intubation and increased mortality. In the present review, we analyze the available clinical and experimental evidence supporting the existence of lung injury caused by uncontrolled high inspiratory effort, we discuss the pathophysiological mechanisms by which increased effort causes P-SILI, and, finally, we consider the measurements and interpretation of bedside physiological measures of increased drive that should alert the clinician. The data presented in this review could help to recognize injurious respiratory patterns that may trigger P-SILI and to prevent it.

Family-centered interventions and patient outcomes in the adult intensive care unit: A systematic review of randomized controlled trials.

OBJECTIVE: There is a need to understand how family engagement in the intensive care unit (ICU) impacts patient outcomes. We reviewed the literature for randomized family-centered interventions with patient-related outcomes in the adult ICU. DATA SOURCES: The MEDLINE, EMBASE, PsycINFO, CINAHL, and the Cochrane Library databases were searched from inception until July 3, 2023. STUDY SELECTION: Articles involving randomized controlled trials (RCTs) in the adult critical care setting evaluating family-centered interventions and reporting patient-related outcomes. DATA EXTRACTION: Author, publication year, setting, number of participants, intervention category, intervention, and patient-related outcomes (patient-reported, physiological, clinical) were extracted. DATA SYNTHESIS: There were 28 RCTs (12,174 participants) included. The most common intervention types were receiving care and meeting needs (N = 10) and family presence (N = 7). 16 RCTs (57%) reported ≥1 positive outcome from the intervention; no studies reported worse outcomes. Studies reported improvements in patient-reported outcomes such as anxiety, satisfaction, post-traumatic stress symptoms, depression, and health-related quality of life. RCTs reported improvements in physiological indices, adverse events, mechanical ventilation duration, analgesia use, ICU length of stay, delirium, and time to withdrawal of life-sustaining treatments. CONCLUSIONS: Nearly two-thirds of RCTs evaluating family-centered interventions in the adult ICU reported positive patient-related outcomes. KEYPOINTS: Question: Do family-centered interventions improve patient outcomes in the adult intensive care unit (ICU)? FINDINGS: The systematic review found that nearly two-thirds of randomized clinical trials of family-centered interventions in the adult ICU improved patient outcomes. Studies found improvements in patient mental health, care satisfaction, physiological indices, and clinical outcomes. There were no studies reporting worse patient outcomes. Meaning: Many family-centered interventions can improve patient outcomes.

Understanding cardiopulmonary interactions through esophageal pressure monitoring.

Esophageal pressure is the closest estimate of pleural pressure. Changes in esophageal pressure reflect changes in intrathoracic pressure and affect transpulmonary pressure, both of which have multiple effects on right and left ventricular performance. During passive breathing, increasing esophageal pressure is associated with lower venous return and higher right ventricular afterload and lower left ventricular afterload and oxygen consumption. In spontaneously breathing patients, negative pleural pressure swings increase venous return, while right heart afterload increases as in passive conditions; for the left ventricle, end-diastolic pressure is increased potentially favoring lung edema. Esophageal pressure monitoring represents a simple bedside method to estimate changes in pleural pressure and can advance our understanding of the cardiovascular performance of critically ill patients undergoing passive or assisted ventilation and guide physiologically personalized treatments.

Pathophysiology and Clinical Meaning of Ventilation-Perfusion Mismatch in the Acute Respiratory Distress Syndrome.

Acute respiratory distress syndrome (ARDS) remains an important clinical challenge with a mortality rate of 35-45%. It is being increasingly demonstrated that the improvement of outcomes requires a tailored, individualized approach to therapy, guided by a detailed understanding of each patient's pathophysiology. In patients with ARDS, disturbances in the physiological matching of alveolar ventilation (V) and pulmonary perfusion (Q) (V/Q mismatch) are a hallmark derangement. The perfusion of collapsed or consolidated lung units gives rise to intrapulmonary shunting and arterial hypoxemia, whereas the ventilation of non-perfused lung zones increases physiological dead-space, which potentially necessitates increased ventilation to avoid hypercapnia. Beyond its impact on gas exchange, V/Q mismatch is a predictor of adverse outcomes in patients with ARDS; more recently, its role in ventilation-induced lung injury and worsening lung edema has been described. Innovations in bedside imaging technologies such as electrical impedance tomography readily allow clinicians to determine the regional distributions of V and Q, as well as the adequacy of their matching, providing new insights into the phenotyping, prognostication, and clinical management of patients with ARDS. The purpose of this review is to discuss the pathophysiology, identification, consequences, and treatment of V/Q mismatch in the setting of ARDS, employing experimental data from clinical and preclinical studies as support.

Expert opinion document: "Electrical impedance tomography: applications from the intensive care unit and beyond".

Mechanical ventilation is a life-saving technology, but it can also inadvertently induce lung injury and increase morbidity and mortality. Currently, there is no easy method of assessing the impact that ventilator settings have on the degree of lung inssflation. Computed tomography (CT), the gold standard for visually monitoring lung function, can provide detailed regional information of the lung. Unfortunately, it necessitates moving critically ill patients to a special diagnostic room and involves exposure to radiation. A technique introduced in the 1980s, electrical impedance tomography (EIT) can non-invasively provide similar monitoring of lung function. However, while CT provides information on the air content, EIT monitors ventilation-related changes of lung volume and changes of end expiratory lung volume (EELV). Over the past several decades, EIT has moved from the research lab to commercially available devices that are used at the bedside. Being complementary to well-established radiological techniques and conventional pulmonary monitoring, EIT can be used to continuously visualize the lung function at the bedside and to instantly assess the effects of therapeutic maneuvers on regional ventilation distribution. EIT provides a means of visualizing the regional distribution of ventilation and changes of lung volume. This ability is particularly useful when therapy changes are intended to achieve a more homogenous gas distribution in mechanically ventilated patients. Besides the unique information provided by EIT, its convenience and safety contribute to the increasing perception expressed by various authors that EIT has the potential to be used as a valuable tool for optimizing PEEP and other ventilator settings, either in the operative room and in the intensive care unit. The effects of various therapeutic interventions and applications on ventilation distribution have already been assessed with the help of EIT, and this document gives an overview of the literature that has been published in this context.

Awake Venovenous Extracorporeal Membrane Oxygenation for Coronavirus Disease 2019 Acute Respiratory Failure.

Implantation of venovenous extracorporeal membrane oxygenation as an alternative to invasive mechanical ventilation, an "awake approach," may facilitate a lung- and diaphragm-protective ventilatory strategies without the associated harms of endotracheal intubation, positive pressure ventilation, and continuous sedation. This report presents the characteristics and outcomes of the patients treated with the awake venovenous extracorporeal membrane oxygenation approach. DESIGN: Retrospective case series. SETTING: Monocenter study. PATIENTS: Severe acute respiratory syndrome coronavirus 2 patients with acute respiratory failure treated with venovenous extracorporeal membrane oxygenation instead of invasive mechanical ventilation from March 2020 to March 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Physiologic and laboratory data were collected at admission to the ICU, prior to and after venovenous extracorporeal membrane oxygenation implantation, and at decannulation. Seven patients were treated with venovenous extracorporeal membrane oxygenation instead of invasive mechanical ventilation due to hypoxemia with a median Pao2/Fio2 ratio at implantation of 76 (interquartile range, 59-92). Four patients in the awake group subsequently required invasive mechanical ventilation, and only one patient (14.3%) died. There were no significant complications attributed venovenous extracorporeal membrane oxygenation. CONCLUSIONS: This report demonstrates that in a selected group of patients, an "awake" venovenous extracorporeal membrane oxygenation approach is feasible and may result in favorable outcomes.