Lung Recruitment Research Articles

Correlation between the hysteresis of the pressure–volume curve and the recruitment-to-inflation ratio in patients with coronavirus disease 2019

BackgroundSince the response to lung recruitment varies greatly among patients receiving mechanical ventilation, lung recruitability should be assessed before recruitment maneuvers. The pressure–volume curve (PV curve) and recruitment-to-inflation ratio (R/I ratio) can be used bedside for evaluating lung recruitability and individualing positive end-expiratory pressure (PEEP). Lung tissue recruitment on computed tomography has been correlated with normalized maximal distance (NMD) of the quasi-static PV curve. NMD is the maximal distance between the inspiratory and expiratory limb of the PV curve normalized to the maximal volume. However, the relationship between the different parameters of hysteresis of the quasi-static PV curve and R/I ratio for recruitability is unknown.MethodsWe analyzed the data of 33 patients with severe coronavirus disease 2019 (COVID-19) who received invasive mechanical ventilation. Respiratory waveform data were collected from the ventilator using proprietary acquisition software. We examined the relationship of the R/I ratio, quasi-static PV curve items such as NMD, and respiratory system compliance (Crs).ResultsThe median R/I ratio was 0.90 [interquartile range (IQR), 0.70–1.15] and median NMD was 41.0 [IQR, 37.1–44.1]. The NMD correlated significantly with the R/I ratio (rho = 0.74, P < 0.001). Sub-analysis showed that the NMD and R/I ratio did not correlate with Crs at lower PEEP (− 0.057, P = 0.75; and rho = 0.15, P = 0.41, respectively). On the contrary, the ratio of Crs at higher PEEP to Crs at lower PEEP (Crs ratio (higher/lower)) moderately correlated with NMD and R/I ratio (rho = 0.64, P < 0.001; and rho = 0.67, P < 0.001, respectively).ConclusionsNMD of the quasi-static PV curve and R/I ratio for recruitability assessment are highly correlated. In addition, NMD and R/I ratio correlated with the Crs ratio (higher/lower). Therefore, NMD and R/I ratio could be potential indicators of recruitability that can be performed at the bedside.

Intrapulmonary percussive ventilation for children with bronchiolitis on non-Invasive Ventilation support

Objective: Pediatric Intensive Care (PICU) admission of children with bronchiolitis as well as the use of Non-Invasive Ventilation (NIV) are increasing. The current treatment for bronchiolitis is supportive, and there are no specific studies addressing this group of severe bronchiolitis patients supported with NIV. Intrapulmonary Percussive Ventilation (IPV) is a lung recruitment physical therapy technique used in our PICU to augment lung aeration and improve gas exchange. We hypothesized that IPV treatment can be used to improve the clinical course of infants on NIV support suffering from bronchiolitis. Design: A prospective, open, randomized study. Setting: Single-center Pediatric ICU Patients: Children less than 2 years old admitted to our PICU between November 2016 and April 2018 with a diagnosis of bronchiolitis who were prescribed noninvasive positive pressure ventilation as their sole respiratory treatment modality Interventions: Patients were randomly assigned to two intervention groups: IPV vs. control (standard treatment). Measurements and main results: Thirty-eight infants with bronchiolitis treated with NIV support were randomized into two groups. The probability of a superior outcome (less chance of invasive mechanical ventilation and fewer PICU days) was 62.7% (95% CI, 45%-77%, p = 0.18) in the IPV group compared to the control group. Among the IPV group, there were no failures that required intubation in comparison to three intubations (13.6%) among the control group (p = 0.24). For the IPV group, the PICU length of stay (LOS) was 4.13 ± 2.45 days, compared to 6.18 ± 4.72 for the inhalation group. This difference was not statistically significant. Conclusions: In this single-center study, the use of IPV had no adverse reactions. The study failed to show a statistically significant effect of IPV treatment on the course of hospitalization of patients with bronchiolitis on NIV support in the PICU. Trial registration: Clinical Trials.gov NCT03037801.

Left Ventricular Diastolic Dysfunction in ARDS Patients.

Background: The aim of this study was to evaluate the possible presence of diastolic dysfunction and its possible effects in terms of respiratory mechanics, gas exchange and lung recruitability in mechanically ventilated ARDS. Methods: Consecutive patients admitted in intensive care unit (ICU) with ARDS were enrolled. Echocardiographic evaluation was acquired at clinical PEEP level. Lung CT-scan was performed at 5 and 45 cmH2O. In the study, 2 levels of PEEP (5 and 15 cmH2O) were randomly applied. Results: A total of 30 patients were enrolled with a mean PaO2/FiO2 and a median PEEP of 137 ± 52 and 10 [9–10] cmH2O, respectively. Of those, 9 patients (30%) had a diastolic dysfunction of grade 1, 2 and 3 in 33%, 45% and 22%, respectively, without any difference in gas exchange and respiratory mechanics. The total lung weight was significantly higher in patients with diastolic dysfunction (1669 [1354–1909] versus 1554 [1146–1942] g) but the lung recruitability was similar between groups (33.3 [27.3–41.4] versus 30.6 [20.0–38.8] %). Left ventricular ejection fraction (57 [39–62] versus 60 [57–60]%) and TAPSE (20.0 [17.0–24.0] versus 24.0 [20.0–27.0] mL) were similar between the two groups. The response to changes of PEEP from 5 to 15 cmH2O in terms of oxygenation and respiratory mechanics was not affected by the presence of diastolic dysfunction. Conclusions: ARDS patients with left ventricular diastolic dysfunction presented a higher amount of lung edema and worse outcome.

Positive- and Negative-Pressure Ventilation Characterized by Local and Global Pulmonary Mechanics.

Rationale: There is continued debate regarding the equivalency of positive-pressure ventilation (PPV) and negative-pressure ventilation (NPV). Resolving this question is important because of the different practical ramifications of the two paradigms. Objectives: We sought to investigate the parallel between PPV and NPV and determine whether or not these two paradigms cause identical ventilation profiles by analyzing the local strain mechanics when the global tidal volume (Vt) and inflation pressure was matched. Methods: A custom-designed electromechanical apparatus was used to impose equal global loads and displacements on the same ex vivo healthy porcine lung using PPV and NPV. High-speed high-resolution cameras recorded local lung surface deformations and strains in real time, and differences between PPV and NPV global energetics, viscoelasticity, as well as local tissue distortion were assessed. Measurements and Main Results: During initial inflation, NPV exhibited significantly more bulk pressure-volume compliance than PPV, suggestive of earlier lung recruitment. NPV settings also showed reduced relaxation, hysteresis, and energy loss compared with PPV. Local strain trends were also decreased in NPV, with reduced tissue distortion trends compared with PPV, as revealed through analysis of tissue anisotropy. Conclusions: Apparently, contradictory previous studies are not mutually exclusive. Equivalent changes in transpulmonary pressures in PPV and NPV lead to the same changes in lung volume and pressures, yet local tissue strains differ between PPV and NPV. Although limited to healthy specimens and ex vivo experiments in the absence of a chest cavity, these results may explain previous reports of better oxygenation and less lung injury in NPV.

The Social Economic Return of a Positive End-Expiratory Pressure–Based Lung Recruitment Clinical Trial Program in Patients With Acute Respiratory Distress Syndrome

ObjectivesThis study aimed to estimate the socioeconomic return from the value of lives saved by the protocol indicated by the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART). ART was conducted through a multicenter randomized trial at 120 intensive care units from 9 countries, enrolling adults with moderate to severe acute respiratory distress syndrome. It investigated whether lung recruitment associated with positive end-expiratory pressure titration according to the best respiratory system compliance decreases 28-day mortality of patients compared with a conventional low-positive end-expiratory pressure strategy. MethodsThe value of lives saved was estimated by considering whether the trial findings were implemented in the eligible patient populations for 1 year, and then the social economic return was computed by subtracting the clinical trial costs from the gross benefit. The return was computed by subtracting the ART costs from its gross benefit. ResultsThe ART net benefit is approximately 152 million dollars if it is implemented in 50% of eligible patients in Brazil under the baseline assumptions. For every dollar spent in the clinical trial, a return of 114 dollars was achieved in Brazil alone. If the trial findings are implemented in all eligible patients, then the trial return would be 229.5 dollars for every dollar invested with a net benefit of 304 million dollars. ConclusionsThese findings highlight the substantial economic benefit of clinical trials on acute respiratory distress syndrome treatments for society. It also points out that the public return of clinical trials can be potentialized when the new trial findings are fully implemented on eligible patients.

Prone positioning may increase lung overdistension in COVID-19-induced ARDS

Real-time effects of changing body position and positive end-expiratory pressure (PEEP) on regional lung overdistension and collapse in individual patients remain largely unknown and not timely monitored. The aim of this study was to individualize PEEP in supine and prone body positions seeking to reduce lung collapse and overdistension in mechanically ventilated patients with coronavirus disease (COVID-19)-induced acute respiratory distress syndrome (ARDS). We hypothesized that prone positioning with bedside titrated PEEP would provide attenuation of both overdistension and collapse. In this prospective observational study, patients with COVID-19-induced ARDS under mechanical ventilation were included. We used electrical impedance tomography (EIT) with decremental PEEP titration algorithm (PEEPEIT-titration), which provides information on regional lung overdistension and collapse, along with global respiratory system compliance, to individualize PEEP and body position. PEEPEIT-titration in supine position followed by PEEPEIT-titration in prone position were performed. Immediately before each PEEPEIT-titration, the same lung recruitment maneuver was performed: 2 min of PEEP 24 cmH2O and driving pressure of 15 cmH2O. Forty-two PEEPEIT-titration were performed in ten patients (21 pairs supine and prone positions). We have found larger % of overdistension along the PEEP titration in prone than supine position (P = 0.042). A larger % of collapse along the PEEP titration was found in supine than prone position (P = 0.037). A smaller respiratory system compliance was found in prone than supine position (P < 0.0005). In patients with COVID-19-induced ARDS, prone body position, when compared with supine body position, decreased lung collapse at low PEEP levels, but increased lung overdistension at PEEP levels greater than 10 cm H2O.Trial registration number: NCT04460859.

Association of radiological lung pattern and respiratory mechanics with potential for lung recruitment in patients with COVID–ARDS: a retrospective cohort study

BackgroundThe ventilatory management of COVID–ARDS is controversial, especially with regard to the different subtypes and associated PEEP titration. A higher PEEP may be beneficial only in patients with potential for lung recruitment. The assessment of lung recruitment may be guided by lung imaging, such as electric impedance tomography or recruitment computed tomography, but is complex and not established in routine clinical practice. Therefore, bedside identification of recruitable ARDS phenotypes can aid in PEEP titration in clinical settings.MethodsIn this retrospective consecutive cohort study in 40 patients with moderate-to-severe COVID–ARDS, we assessed lung recruitment using the recruitment-to-inflation ratio (R/I) in moderate-to-severe COVID–ARDS. Evidence of recruitment (R/I ≥ 0.5) was compared between clinical and computed tomography data.ResultsOf the included patients, 28 (70%) were classified as recruiters by the R/I. Lung recruitment was associated with higher compliance and was not associated with a consolidated lung pattern assessed using CT. Even in the tertile of patients with the highest compliance (37–70 ml/mbar), eight (73%) patients were classified as recruitable. Patients classified as recruitable presented a lower reticular lung pattern (2% vs. 6%, p = 0.032).ConclusionsPrediction of lung recruitment is difficult based on routine clinical data but may be improved by assessment of radiographic lung patterns. A bedside assessment of recruitment is necessary to guide clinical care. Even a high compliance may not rule out the potential for lung recruitment.

Effect of electrical impedance-guided PEEP in reducing pulmonary complications after craniotomy: study protocol for a randomized controlled trial

ObjectiveThe purpose of this study is to explore whether electrical impedance tomography (EIT)-guided individualized positive end-expiratory pressure (PEEP) can reduce the incidence of pulmonary complications within 1 week following a craniotomy compared with a single PEEP (PEEP = 6 cmH2O) from dura suturing to extubation.MethodsA randomized controlled trial will be conducted at the Second Affiliated Hospital of Soochou University. Five hundred forty patients undergoing a craniotomy in the supine position will be randomly allocated into the P6 (PEEP = 6 cmH2O) or Pi (individualized PEEP) group. Both groups of patients will receive a lung recruitment maneuver before suturing the dura. Then, the P6 group will receive 6 cmH2O PEEP, and the Pi group will receive EIT-guided individualized PEEP. The incidence and severity score of pulmonary complications within 1 week following surgery, the lung ultrasound score (LUS), regional cerebral oxygen saturation (rScO2), and PaO2/FiO2 before anesthesia (T0), 10 min after extubation (T1), 24 h after extubation (T2), and 72 h after extubation (T3) will be compared between the two groups. The duration of surgery and anesthesia, the level and duration of PEEP during surgery, the volume of liquid intake and output during surgery, and the postoperative ICU and hospital stays will be recorded. The main outcome of this study will be the incidence of pulmonary complications within 1 week after surgery.DiscussionThe purposes of this study are to determine whether EIT-guided individualized PEEP from the beginning of dura suturing to extubation reduces the incidence of pulmonary complications within 1 week after a craniotomy compared with a single constant PEEP and to evaluate the length of ICU and hospital stays. If our results are positive, this study will show that EIT-guided individualized PEEP is better than a single constant PEEP and can further improve the prognosis of neurosurgical patients and reduce hospitalization costs, which will promote the wide application of individualized PEEP in clinical anesthesia.Trial registrationChinese Clinical Trial Registry CHiCTR2100051200. Registered on 15 September 2021.

Role of Lung Recruitment Maneuvers in Elderly Post-operative Upper Abdominal Surgery

Role of Lung Recruitment Maneuvers in Elderly Post-operative Upper Abdominal Surgery

Implementation of a Revised Montpellier Bundle on the Outcome of Intubation in Critically Ill Patients: A Quality Improvement Project.

The feasibility of implementing a revised Montpellier intubation bundle incorporating recent evidences was tested in a quality-improvement project. It was hypothesized that this "Care Bundle" implementation would reduce intubation-related complications. The project was conducted in an 18-bedded multidisciplinary intensive care unit (ICU). Baseline data for intubations were collected over 3-month "Control Period". During the 2-month "Interphase", a revised intubation bundle was developed, and staff members involved in the intubation process were extensively trained on different aspects of intubation with emphasis on bundle components. Various components of the bundle were pre-intubation fluid loading, pre-oxygenation with NIV plus PS, positive-pressure ventilation post-induction, succinylcholine as a first-line induction agent, routine use of stylet, and lung recruitment within 2 minutes of intubation. Intubation data were collected again in the 3-month "Intervention Period". Data were collected for 61 and 64 intubations, respectively, during control and intervention periods. There was significant improvement in compliance to five of six-bundle components; improvement in pre-intubation fluid loading during the intervention period did not reach statistical significance. Overall, at least 3 components of the bundle were complied within over 92% of intubations in the intervention period. However, whole-bundle compliance was limited to 14.3%. Incidences of major complications were reduced significantly in the intervention period (23.8% vs 45.9%, p = 0.01). There was significant reduction in profound hypotension (21.77% vs 29.51%, p = 0.04) and a nonsignificant 11.89% reduction in profound hypoxemia. There were no differences in minor complications. Implementation of an evidence-based revised Montpellier intubation bundle is feasible and it reduces major complications related to endotracheal intubation. Ghosh S, Salhotra R, Arora G, Lyall A, Singh A, Kumar N, et al. Implementation of a Revised Montpellier Bundle on the Outcome of Intubation in Critically Ill Patients: A Quality Improvement Project. Indian J Crit Care Med 2022;26(10):1106-1114.

5-Methoxyflavone-induced AMPKα activation inhibits NF-κB and P38 MAPK signaling to attenuate influenza A virus-mediated inflammation and lung injury in vitro and in vivo

Influenza-related acute lung injury (ALI) is a life-threatening condition that results mostly from uncontrolled replication of influenza virus (IV) and severe proinflammatory responses. The methoxy flavonoid compound 5-methoxyflavone (5-MF) is believed to have superior biological activity in the treatment of cancer. However, the effects and underlying mechanism of 5-MF on IV-mediated ALI are still unclear. Here, we showed that 5-MF significantly improved the survival of mice with lethal IV infection and ameliorated IV-mediated lung edema, lung histological changes, and inflammatory cell lung recruitment. We found that 5-MF has antiviral activity against influenza A virus (IAV), which was probably associated with increased expression of radical S-adenosyl methionine domain containing 2 (RSAD2) and suppression of endosomal acidification. Moreover, IV-infected A549 cells with 5-MF treatment markedly reduced proinflammatory mediator expression (IL-6, CXCL8, TNF-α, CXCL10, CCL2, CCL3, CCL4, GM-CSF, COX-2, and PGE2) and prevented P-IKBα, P-P65, and P-P38 activation. Interestingly, we demonstrated that 5-MF treatment could trigger activation of AMP-activated protein kinase (AMPK)α in IV-infected A549 cells, as evidenced by activation of the AMPKα downstream molecule P53. Importantly, the addition of AMPKα blocker compound C dramatically abolished 5-MF-mediated increased levels of RSAD2, the inhibitory effects on H1N1 virus-elicited endosomal acidification, and the suppression expression of proinflammatory mediators (IL-6, TNF-α, CXCL10, COX-2 and PGE2), as well as the inactivation of P-IKBα, P-P65, and P-P38 MAPK signaling pathways. Furthermore, inhibition of AMPKα abrogated the protective effects of 5-MF on H1N1 virus-mediated lung injury and excessive inflammation in vivo. Taken together, these results indicate that 5-MF alleviated IV-mediated ALI and suppressed excessive inflammatory responses through activation of AMPKα signaling.

Quantitative lung ultrasound detects dynamic changes in lung recruitment in the preterm lamb

BackgroundLung ultrasound (LUS) may not detect small, dynamic changes in lung volume. Mean greyscale measurement using computer-assisted image analysis (Q-LUSMGV) may improve the precision of these measurements.MethodsPreterm lambs (n = 40) underwent LUS of the dependent or non-dependent lung during static pressure–volume curve mapping. Total and regional lung volumes were determined using the super-syringe technique and electrical impedance tomography. Q-LUSMGV and gold standard measurements of lung volume were compared in 520 images.ResultsDependent Q-LUSMGV moderately correlated with total lung volume (rho = 0.60, 95% CI 0.51–0.67) and fairly with right whole (rho = 0.39, 0.27–0.49), central (rho = 0.38, 0.27–0.48), ventral (rho = 0.41, 0.31–0.51) and dorsal regional lung volumes (rho = 0.32, 0.21–0.43). Non-dependent Q-LUSMGV moderately correlated with total lung volume (rho = 0.57, 0.48–0.65) and fairly with right whole (rho = 0.43, 0.32–0.52), central (rho = 0.46, 0.35–0.55), ventral (rho = 0.36, 0.25–0.47) and dorsal lung volumes (rho = 0.36, 0.25–0.47). All correlation coefficients were statistically significant. Distinct inflation and deflation limbs, and sonographic pulmonary hysteresis occurred in 95% of lambs. The greatest changes in Q-LUSMGV occurred at the opening and closing pressures.ConclusionQ-LUSMGV detected changes in total and regional lung volume and offers objective quantification of LUS images, and may improve bedside discrimination of real-time changes in lung volume.ImpactLung ultrasound (LUS) offers continuous, radiation-free imaging that may play a role in assessing lung recruitment but may not detect small changes in lung volume.Mean greyscale image analysis using computer-assisted quantitative LUS (Q-LUSMGV) moderately correlated with changes in total and regional lung volume.Q-LUSMGV identified opening and closing pressure and pulmonary hysteresis in 95% of lambs.Computer-assisted image analysis may enhance LUS estimation of lung recruitment at the bedside.Future research should focus on improving precision prior to clinical translation.

Observation of Curative Effect of Lung Recruitment in Patients with Acute Respiratory Distress Syndrome after Cardiopulmonary Bypass Surgery.

Recruitment maneuver (RM) has become a routine supplementary maneuver for clinical rescue of severe ARDS with low tidal volume/pressure-limited mechanical ventilation. Recruitment of patients with ARDS mechanical ventilation can improve the lung compliance, promote the opening of collapsed alveoli, improve the ratio of ventilation to blood flow, reduce dead space, reduce shunt flow, and improve oxygenation function. In this paper, the patients were divided into lung recruitment group and conventional treatment group by the random number permutation table method. When the patient's percutaneous oxygen saturation is less than or equal to 88%, the partial pressure of oxygen in the arterial blood gas is less than or equal to 55 mmHg, or the ventilator tube is disconnected during sputum suction or other accidents, a CPAP × 60 − second lung recruitment maneuver is required. Then adjust the ventilator parameters in the same way. In the process of lung recruitment, the changes in invasive continuous arterial blood pressure will also be observed. If the blood pressure dropped to ≤90/60 mmHg, one recruitment maneuver was terminated in advance. And both groups of patients used the Dräger- or PB840-imported multifunctional ventilator. The treatment of primary disease and predisposing factors, fluid management strategies, antibiotics and glucocorticoids, nutrition, and metabolic support in the two groups of patients in the study were the same. The PaO2/FiO2 value improved by 51% 10 minutes after recruitment, and the median increased from 111 (IQR, 73-265) before recruitment to 170 (IQR, 102-340) (P < 0.01), the improvement of PaO2/FiO2 at 4 hours after recruitment and 12 hours after recruitment was 78% (P < 0.05) and 39% (P < 0.01), respectively, and the median PaO2/FiO2 at 4 hours after recruitment was 198 (IQR, 116-256). The median PaO2/FiO2 became 155 (IQR, 127-235) 12 hours after recruitment. Recruitment can reduce the accumulation of neutrophils in lung tissue, reduce the release of inflammatory factors, reduce pulmonary edema, and reduce pathological damage.

A Novel Agnostic Respiratory Stimulant as a Treatment for Apnea of Prematurity: A Proof-of-Concept Study.

Aim/Objective: ENA-001 is a novel selective antagonist of large-conductance BK (big potassium) channels located in the carotid bodies, where they act as chemoreceptors that sense low arterial oxygen levels and establish a feedback loop to brainstem nuclei responsible for initiating spontaneous breathing and maintaining adequate oxygen to tissues. ENA-001 attenuates respiratory depression induced by a variety of chemical agents, essentially "agnostic" to the precipitating drug (e.g., opioid(s), benzodiazepine, alcohol, or propofol). But it had not been tested against respiratory depression resulting from a physiological cause, such as apnea of prematurity (AOP). This proof-of-principle study used a well-described animal model (premature lamb) to test the effectiveness of ENA-001 in the setting of an under-developed respiratory control system, similar to that in human AOP.Materials and Methods: A set of twin lambs was delivered prematurely via caesarian section at 135 ± 2 d gestational age (GA). An arterial catheter was connected to a transducer for pressure monitoring and a venous catheter was connected to a pump for continuous infusion of 5% dextrose in water (D5W). Lambs were to receive four mechanical breaths for lung recruitment and then started on continuous positive airway pressure (CPAP). After a stabilization period of 15 minutes, the protocol called for the first lamb to be started on continuous infusion of ENA-001, with ascending dose hourly (0.4, 1.1, 2.0, 12.0 mg/kg/hr), while the second lamb was to serve as a sham (D5W) control. At least 10 representative breaths free of artifact from motion or atypical breaths were recorded using a pulmonary function system designed for neonatal research. To maintain a stable plane of anesthesia, repeat doses of fentanyl (1 µg IM) were given as needed based on blood pressure response to stimulation.Results: Two male lambs were delivered. Unexpectedly, neither lamb exhibited a drive for spontaneous breathing. Each required manual ventilation, with a complete absence of spontaneous effort. Despite the poor prognosis owing to the absence of ventilatory effort, continuous infusion of the first dose of ENA-001 was started 20 minutes after birth. The test animal continued to require manual ventilation, which was continued for an additional 10 minutes. An intravenous (IV) bolus of ENA-001 was given. Nearly instantaneously following the delivery of the IV bolus, the lamb began breathing spontaneously and did not require manual intervention for the remainder of the study. The sham animal was delivered approximately an hour following the test animal. As with the test animal, the sham animal lacked spontaneous breathing efforts. A decision was made to manually ventilate for 30 minutes to match the course for the test animal. At the 30-minute time point, an IV bolus infusion of ENA-001 was delivered. Nearly instantaneously following the delivery of the IV bolus, the lamb began breathing spontaneously. After several minutes, the spontaneous breathing efforts abated, and manual ventilation was resumed. The animal was then sacrificed for tissue harvest.Conclusion: These results suggest that ENA-001 might be an effective therapy, alone or as a co-medication, for the treatment of AOP. They further suggest that ENA-001 might have broader applications in situations of neurological ventilatory insufficiency.

Evolution of respiratory system compliance and potential for lung recruitment in COVID-19–induced acute respiratory distress syndrome

BackgroundCoronavirus disease 2019 (COVID-19) has been frequently complicated by severe acute respiratory distress syndrome (ARDS) with prolonged invasive ventilation. While respiratory system compliance and lung recruitability have been described within the first days after ICU admission, data about their longitudinal changes are still limited. Therefore, we conducted this study to assess the evolution of respiratory system compliance and lung recruitability in patients with COVID-19–related ARDS. MethodWe conducted a prospective single-center study in patients admitted for COVID-19–related ARDS during the first wave of the pandemic, from March 16, 2020 to April 10, 2020. Respiratory system compliance was calculated daily at clinical positive end-expiratory pressure (PEEP) during passive breathing. The potential for lung recruitment was assessed by measuring the volume derecruited between PEEP 15 cmH2O and 5 cmH2O, and using the calculation of the recruitment-to-inflation ratio (R/I ratio). Recruitable lung was considered when the R/I ratio was at least 0.5. The primary outcome was the evolution of respiratory mechanics over time. The secondary outcome was the evolution of lung recruitability over time. ResultsThirty-two patients were included in this study. The respiratory mechanics were assessed 222 times (7 ± 5 times per patient). Respiratory system compliance at clinical PEEP was 29.1 mL/cmH2O (interquartile range [IQR]: 24.1–33.9 mL/cmH2O) and decreased significantly over time (P <0.0001). Lung recruitability was assessed in 22 out of the 32 patients (60 assessments). The median volume derecruited between PEEP 15 cmH2O and 5 cmH2O was 246.8 mL (IQR: 180.8–352.2 mL) and the median R/I ratio was 0.56 (IQR: 0.39–0.73). Neither changed significantly over time. The proportion of patients with recruitable lung was 50.0% (6/12) within the first 3 days after intubation, 69.2% (9/13) between day 4 and day 7, and 66.7% (8/12) after day 7 (P=0.7934). ConclusionsIn our cohort, respiratory system compliance was low and decreased over time. The potential for lung recruitment was high and persisted despite prolonged mechanical ventilation, suggesting that maintaining high PEEP levels in the later course of COVID-19 could be adequate.

P1.01: Optimizing Lung Function During Donor Management Through A Multidisciplinary Approach

Introduction: In current healthcare, a multi-disciplinary approach is taken in critical care to ensure all specialties can offer their training and expertise in the care of every patient. In organ donation, and specifically donor management, having a team of Procurement Transplant Coordinators (PTCs) that is comprised similarly ensures that optimal results can be achieved through a varied knowledge base. Traditionally, this has been heavily weighted with Registered Nurses with critical care experience. We propose that including Registered Respiratory Therapists (RRTs) as PTCs can broaden the base of expertise of the team and maximize successful lung transplantation. Additionally, the incorporation of different modes and modalities of ventilation with a physiological approach to lung recruitment has successfully proven an increase in lung optimization. Method: To fully understand the positive impact of RRTs in lung recruitment, we looked at the upward trend of the Horowitz index for Lung Function (P/F ratio) with a subject United States based Organ Procurement Organization and how it correlated with an increasing number of PTCs that are licensed and registered Respiratory Therapists. Four RRTs were onboarded to the donor management team during 2020 and 2021. Comparing the results from previous years, data showed a related increase in lung recruitment and optimization per year with RRTs working as PTCs. Results: Evidence demonstrated a correlation of the increase in lung procurement and transplantation numbers mirroring an increase in RRTs in the role of PTCs. Improvements to P/F ratios were compared at the beginning of the case to the final P/F ratio prior to OR. From January 1, 2018-December 31, 2019 there were 89 donors who were brought to the operating room for lung procurement with the intent of transplant. The median and mean improvement to P/F ratios were +0.83 and +0.83, respectively. From January 1, 2020- December 31, 2021 there were 75 donors who were brought to the operating room for lung procurement with the intent of transplant. The median and mean improvement to P/F ratios were +1.04 and +1.32, respectively. This proved a 25.3% increase for the median PF ratio and a 59% increase to the mean PF ratio. Conclusion: Our research supports that PTCs who are licensed and experienced Respiratory Therapists being proficient in lung physiology, recruitment, and ventilation strategies contribute to an increase in lung optimization. With having specific organ expertise, RRTs have proven to be a vital asset while sharing knowledge with the entire multi-disciplinary team.

Genetically engineered exosomes for targetedly preventing premetastatic niche formation and suppressing postoperative melanoma lung metastasis

Premetastatic niche (PMN) is a prerequisite for initiation of tumor metastasis. Targeting prevention of PMN formation in distant organs is becoming a promising strategy to suppress metastasis of primary tumor. Based on “organotropic metastasis”, melanoma tends to metastasize to lungs, where granulocytic myeloid-derived suppressor cells (G-MDSCs) recruitment in lungs significantly contributes to the PMN formation. Herein, functional exosomes (GExoI) were designed to present pulmonary targeting peptide GFE1 on the membrane and load PI3Kγ inhibitor (IPI549) inside, aiming at suppressing postoperative lung metastasis of melanoma. In postoperative mice model, intravenously injected GExoI could significantly accumulate in lungs and release IPI549 to block G-MDSCs recruitment through interfering with CXCLs/CXCR2/PI3Kγ signaling. The increased percentages of CD4+ T cells and CD8+ T cells in lungs could transform microenvironment from immunosuppression to immunostimulation, leading to metastasis inhibition. This study suggests an effective anti-metastasis strategy of targeting prevention of PMN formation through specifically blocking G-MDSCs recruitment.

Variations of pulse pressure and central venous pressure may predict fluid responsiveness in mechanically ventilated patients during lung recruitment manoeuvre: an ancillary study

BackgroundMaintaining a constant driving pressure during a prolonged sigh breath lung recruitment manoeuvre (LRM) from 20 to 45 cmH20 peak inspiratory pressure in mechanically ventilated patients has been shown to be a functional test to predict fluid responsiveness (FR) when using a linear regression model of hemodynamic parameters, such as central venous pressure (CVP) and pulse pressure (PP). However, two important limitations have been raised, the use of high ventilation pressures and a regression slope calculation that is difficult to apply at bedside. This ancillary study aimed to reanalyse absolute variations of CVP (ΔCVP) and PP (ΔPP) values at lower stages of the LRM, (40, 35, and 30 cm H20 of peak inspiratory pressure) for their ability to predict fluid responsiveness.MethodsRetrospective analysis of a prospective study data set in 18 mechanically ventilated patients, in an intensive care unit. CVP, systemic arterial pressure parameters and stroke volume (SV) were recorded during prolonged LRM followed by a 500 mL crystalloid volume expansion. Patients were considered as fluid responders if SV increased more than 10%. Receiver-operating curves (ROC) analysis with the corresponding grey zone approach were performed.ResultsAreas under the ROC to predict fluid responsiveness for ΔCVP and ΔPP were not different between the successive stepwise increase of inspiratory pressures [0.88 and 0.89 for ΔCVP at 45 and 30 cm H20 (P = 0.89), respectively, and 0.92 and 0.95 for ΔPP at 45 and 30 cm H20, respectively (P = 0.51)]. Using a maximum of 30 cmH2O inspiratory pressure during the LRM, ΔCVP and ΔPP had a threshold value to predict fluid responsiveness of 2 mmHg and 4 mmHg, with sensitivities of 89% and 89% and specificities of 67% and 89%, respectively. Combining ΔPP and ΔCVP decreased the proportion of the patients in the grey zone from 28 to 11% and showed a sensitivity of 88% and a specificity of 83%.ConclusionsA stepwise PEEP elevation recruitment manoeuvre of up to 30 cm H20 may predict fluid responsiveness as well as 45 cm H20. The combination of ΔPP and ΔCVP optimizes the categorization of responder and non-responder patients.

Aeration strategy at birth does not impact carotid haemodynamics in preterm lambs

BackgroundThe impact of different respiratory strategies at birth on the preterm lung is well understood; however, concerns have been raised that lung recruitment may impede cerebral haemodynamics. This study aims to examine the effect of three different ventilation strategies on carotid blood flow, carotid artery oxygen content and carotid oxygen delivery.Methods124–127-day gestation apnoeic intubated preterm lambs studied as part of a larger programme primarily assessing lung injury were randomised to positive pressure ventilation with positive end-expiratory pressure (PEEP) 8 cmH2O (No-RM; n = 12), sustained inflation (SI; n = 15) or dynamic PEEP strategy (DynPEEP; maximum PEEP 14 or 20 cmH2O, n = 41) at birth, followed by 90 min of standardised ventilation. Haemodynamic data were continuously recorded, with intermittent arterial blood gas analysis.ResultsOverall carotid blood flow measures were comparable between strategies. Except for mean carotid blood flow that was significantly lower for the SI group compared to the No-RM and DynPEEP groups over the first 3 min (p < 0.0001, mixed effects model). Carotid oxygen content and oxygen delivery were similar between strategies. Maximum PEEP level did not alter cerebral haemodynamic measures.ConclusionsAlthough there were some short-term variations in cerebral haemodynamics between different PEEP strategies and SI, these were not sustained.ImpactDifferent pressure strategies to facilitate lung aeration at birth in preterm infants have been proposed. There is minimal information on the effect of lung recruitment on cerebral haemodynamics.This is the first study that compares the effect of sustained lung inflation and dynamic and static positive end-expiratory pressure on cerebral haemodynamics.We found that the different ventilation strategies did not alter carotid blood flow, carotid oxygen content or carotid oxygen delivery.This preclinical study provides some reassurance that respiratory strategies designed to focus on lung aeration at birth may not impact cerebral haemodynamics in preterm neonates.

Effects of ultrasound-guided alveolar recruitment manoeuvres compared with sustained inflation or no recruitment manoeuvres on atelectasis in laparoscopic gynaecological surgery as assessed by ultrasonography: a randomized clinical trial

BackgroundThe majority of patients may experience atelectasis under general anesthesia, and the Trendelenburg position and pneumoperitoneum can aggravate atelectasis during laparoscopic surgery, which promotes postoperative pulmonary complications. Lung recruitment manoeuvres have been proven to reduce perioperative atelectasis, but it remains controversial which method is optimal. Ultrasonic imaging can be conducive to confirming the effect of lung recruitment manoeuvres. The purpose of our study was to assess the effects of ultrasound-guided alveolar recruitment manoeuvres by ultrasonography on reducing perioperative atelectasis and to check whether the effects of recruitment manoeuvres under ultrasound guidance (visual and semiquantitative) on atelectasis are superior to sustained inflation recruitment manoeuvres (classical and widely used) in laparoscopic gynaecological surgery.MethodsIn this randomized, controlled, double-blinded study, women undergoing laparoscopic gynecological surgery were enrolled. Patients were randomly assigned to receive either lung ultrasound-guided alveolar recruitment manoeuvres (UD group), sustained inflation alveolar recruitment manoeuvres (SI group), or no RMs (C group) using a computer-generated table of random numbers. Lung ultrasonography was performed at four predefined time points. The primary outcome was the difference in lung ultrasound score (LUS) among groups at the end of surgery.ResultsLung ultrasound scores in the UD group were significantly lower than those in both the SI group and the C group immediately after the end of surgery (7.67 ± 1.15 versus 9.70 ± 102, difference, -2.03 [95% confidence interval, -2.77 to -1.29], P < 0.001; 7.67 ± 1.15 versus 11.73 ± 1.96, difference, -4.07 [95% confidence interval, -4.81 to -3.33], P < 0.001;, respectively). The intergroup differences were sustained until 30 min after tracheal extubation (9.33 ± 0.96 versus 11.13 ± 0.97, difference, -1.80 [95% confidence interval, -2.42 to -1.18], P < 0.001; 9.33 ± 0.96 versus 10.77 ± 1.57, difference, -1.43 [95% confidence interval, -2.05 to -0.82], P < 0.001;, respectively). The SI group had a significantly lower LUS than the C group at the end of surgery (9.70 ± 1.02 versus 11.73 ± 1.96, difference, -2.03 [95% confidence interval, -2.77 to -1.29] P < 0.001), but the benefit did not persist 30 min after tracheal extubation.ConclusionsDuring general anesthesia, ultrasound-guided recruitment manoeuvres can reduce perioperative aeration loss and improve oxygenation. Furthermore, these effects of ultrasound-guided recruitment manoeuvres on atelectasis are superior to sustained inflation recruitment manoeuvres.Trial registrationChictr.org.cn, ChiCTR2100042731, Registered 27 January 2021, www.chictr.org.cn.