Project description:BackgroundThe physiological effects of prone ventilation in ARDS patients have been discussed for a long time but have not been fully elucidated. Electrical impedance tomography (EIT) has emerged as a tool for bedside monitoring of pulmonary ventilation and perfusion, allowing the opportunity to obtain data. This study aimed to investigate the effect of prone positioning (PP) on ventilation-perfusion matching by contrast-enhanced EIT in patients with ARDS.DesignMonocenter prospective physiologic study.SettingUniversity medical ICU.PatientsTen mechanically ventilated ARDS patients who underwent PP.InterventionsWe performed EIT evaluation at the initiation of PP, 3 h after PP initiation and the end of PP during the first PP session.Measurements and main resultsThe regional distribution of ventilation and perfusion was analyzed based on EIT images and compared to the clinical variables regarding respiratory and hemodynamic status. Prolonged prone ventilation improved oxygenation in the ARDS patients. Based on EIT measurements, the distribution of ventilation was homogenized and dorsal lung ventilation was significantly improved by PP administration, while the effect of PP on lung perfusion was relatively mild, with increased dorsal lung perfusion observed. The ventilation-perfusion matched region was found to increase and correlate with the increased PaO2/FiO2 by PP, which was attributed mainly to reduced shunt in the lung.ConclusionsProlonged prone ventilation increased dorsal ventilation and perfusion, which resulted in improved ventilation-perfusion matching and oxygenation.Trial registrationClinicalTrials.gov, NCT04725227. Registered on 25 January 2021.
Project description:BackgroundProne position ventilation (PPV) is resource-intensive, yet the optimal strategy for PPV in intubated patients with COVID-19 is unclear.Research questionDoes a prolonged (24 or more h) PPV strategy improve mortality in intubated COVID-19 patients compared with intermittent (∼16 h with daily supination) PPV?Study design and methodsMulticenter, retrospective cohort study of consecutively admitted intubated COVID-19 patients treated with PPV between March 11 and May 31, 2020. The primary outcome was 30-day all-cause mortality. Secondary outcomes included 90-day all-cause mortality and prone-related complications. Inverse probability treatment weights (IPTW) were used to control for potential treatment selection bias.ResultsOf the COVID-19 patients who received PPV, 157 underwent prolonged and 110 underwent intermittent PPV. Patients undergoing prolonged PPV had reduced 30-day (adjusted hazard ratio [aHR], 0.475; 95% CI, 0.336-0.670; P < .001) and 90-day (aHR, 0.638; 95% CI, 0.461-0.883; P = .006) mortality compared with intermittent PPV. In patients with Pao2/Fio2 ≤ 150 at the time of pronation, prolonged PPV was associated with reduced 30-day (aHR, 0.357; 95% CI, 0.213-0.597; P < .001) and 90-day mortality (aHR, 0.562; 95% CI, 0.357-0.884; P = .008). Patients treated with prolonged PPV underwent fewer pronation and supination events (median, 1; 95% CI, 1-2 vs 3; 95% CI, 1-4; P < .001). PPV strategy was not associated with overall PPV-related complications, although patients receiving prolonged PPV had increased rates of facial edema and lower rates of peri-proning hypotension.InterpretationAmong intubated COVID-19 patients who received PPV, prolonged PPV was associated with reduced mortality. Prolonged PPV was associated with fewer pronation and supination events and a small increase in rates of facial edema. These findings suggest that prolonged PPV is a safe, effective strategy for mortality reduction in intubated COVID-19 patients.
Project description:ObjectivesProne positioning allows to improve oxygenation and decrease mortality rate in COVID-19-associated acute respiratory distress syndrome (C-ARDS). However, the mechanisms leading to these effects are not fully understood. The aim of this study is to assess the physiologic effects of pronation by the means of CT scan and electrical impedance tomography (EIT).DesignExperimental, physiologic study.SettingPatients were enrolled from October 2020 to March 2021 in an Italian dedicated COVID-19 ICU.PatientsTwenty-one intubated patients with moderate or severe C-ARDS.InterventionsFirst, patients were transported to the CT scan facility, and image acquisition was performed in prone, then supine position. Back to the ICU, gas exchange, respiratory mechanics, and ventilation and perfusion EIT-based analysis were provided toward the end of two 30 minutes steps (e.g., in supine, then prone position).Measurements and main resultsProne position induced recruitment in the dorsal part of the lungs (12.5% ± 8.0%; p < 0.001 from baseline) and derecruitment in the ventral regions (-6.9% ± 5.2%; p < 0.001). These changes led to a global increase in recruitment (6.0% ± 6.7%; p < 0.001). Respiratory system compliance did not change with prone position (45 ± 15 vs 45 ± 18 mL/cm H2O in supine and prone position, respectively; p = 0.957) suggesting a decrease in atelectrauma. This hypothesis was supported by the decrease of a time-impedance curve concavity index designed as a surrogate for atelectrauma (1.41 ± 0.16 vs 1.30 ± 0.16; p = 0.001). Dead space measured by EIT was reduced in the ventral regions of the lungs, and the dead-space/shunt ratio decreased significantly (5.1 [2.3-23.4] vs 4.3 [0.7-6.8]; p = 0.035), showing an improvement in ventilation-perfusion matching.ConclusionsSeveral changes are associated with prone position in C-ARDS: increased lung recruitment, decreased atelectrauma, and improved ventilation-perfusion matching. These physiologic effects may be associated with more protective ventilation.
Project description:BackgroundProne position has been shown to improve oxygenation and survival in patients with early acute respiratory distress syndrome (ARDS). These beneficial effects are partly mediated by improved ventilation/perfusion (V/Q) distribution. Few studies have investigated the impact of early versus delayed proning on V/Q distribution in patients with ARDS. The aim of this study was to assess the regional ventilation and perfusion distribution in early versus persistent ARDS after prone position.MethodsThis is a prospective, observational study from June 30, 2021, to October 1, 2022 at the medical ICU in Zhongda Hospital, Southeast University. Fifty-seven consecutive adult patients with moderate-to-severe ARDS ventilated in supine and prone position. Electrical impedance tomography was used to study V/Q distribution in the supine position and 12 h after a prone session.ResultsOf the 57 patients, 33 were early ARDS (≤ 7 days) and 24 were persistent ARDS (> 7 days). Oxygenation significantly improved after proning in early ARDS (157 [121, 191] vs. 190 [164, 245] mm Hg, p < 0.001), whereas no significant change was found in persistent ARDS patients (168 [136, 232] vs.177 [155, 232] mm Hg, p = 0.10). Compared to supine position, prone reduced V/Q mismatch in early ARDS (28.7 [24.6, 35.4] vs. 22.8 [20.0, 26.8] %, p < 0.001), but increased V/Q mismatch in persistent ARDS (23.8 [19.8, 28.6] vs. 30.3 [24.5, 33.3] %, p = 0.006). In early ARDS, proning significantly reduced shunt in the dorsal region and dead space in the ventral region. In persistent ARDS, proning increased global shunt. A significant correlation was found between duration of ARDS onset to proning and the change in V/Q distribution (r = 0.54, p < 0.001).ConclusionsProne position significantly reduced V/Q mismatch in patients with early ARDS, while it increased V/Q mismatch in persistent ARDS patients. Trial registration ClinicalTrials.gov (NCT05207267, principal investigator Ling Liu, date of registration 2021.08.20).
Project description:BackgroundThe efficacy and safety profiles of prone ventilation among intubated Coronavirus Disease 2019 (COVID-19) patients remain unclear. The primary objective was to examine the effect of prone ventilation on the ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) in intubated COVID-19 patients.MethodsDatabases of MEDLINE, EMBASE and CENTRAL were systematically searched from inception until March 2021. Case reports and case series were excluded.ResultsEleven studies (n = 606 patients) were eligible. Prone ventilation significantly improved PaO2/FiO2 ratio (studies: 8, n = 579, mean difference 46.75, 95% CI 33.35‒60.15, p < 0.00001; evidence: very low) and peripheral oxygen saturation (SpO2) (studies: 3, n = 432, mean difference 1.67, 95% CI 1.08‒2.26, p < 0.00001; evidence: ow), but not the arterial partial pressure of carbon dioxide (PaCO2) (studies: 5, n = 396, mean difference 2.45, 95% CI 2.39‒7.30, p = 0.32; evidence: very low), mortality rate (studies: 1, n = 215, Odds Ratio 0.66, 95% CI 0.32‒1.33, p = 0.24; evidence: very low), or number of patients discharged alive (studies: 1, n = 43, Odds Ratio 1.49, 95% CI 0.72‒3.08, p = 0.28; evidence: very low).ConclusionProne ventilation improved PaO2/FiO2 ratio and SpO2 in intubated COVID-19 patients. Given the substantial heterogeneity and low level of evidence, more randomized- controlled trials are warranted to improve the certainty of evidence, and to examine the adverse events of prone ventilation.
Project description:RationaleThe prone position is used to improve gas exchange in patients with acute respiratory distress syndrome. However, the regional mechanism by which the prone position improves gas exchange in acutely injured lungs is still incompletely defined.MethodsWe used positron emission tomography imaging of [(13)N]nitrogen to assess the regional distribution of pulmonary shunt, aeration, perfusion, and ventilation in seven surfactant-depleted sheep in supine and prone positions.ResultsIn the supine position, the dorsal lung regions had a high shunt fraction, high perfusion, and poor aeration. The prone position was associated with an increase in lung gas content and with a more uniform distribution of aeration, as the increase in aeration in dorsal lung regions was not offset by loss of aeration in ventral regions. Consequently, the shunt fraction decreased in dorsal regions in the prone position without a concomitant impairment of gas exchange in ventral regions, thus leading to a significant increase in the fraction of pulmonary perfusion participating in gas exchange. In addition, the vertical distribution of specific alveolar ventilation became more uniform in the prone position. A biphasic relation between regional shunt fraction and gas fraction showed low shunt for values of gas fraction higher than a threshold, and a steep linear increase in shunt for lower values of gas fraction.ConclusionIn a surfactant-deficient model of lung injury, the prone position improved gas exchange by restoring aeration and decreasing shunt while preserving perfusion in dorsal lung regions, and by making the distribution of ventilation more uniform.
Project description:While benefits of prone position in mechanically-ventilated patients have been well-described, a randomized-control trial to determine the effects of prone positioning in awake, spontaneously-breathing patients with an acute pneumonia has not been previously conducted. Prone Position and Respiratory Outcomes in Non-Intubated COVID-19 PatiEnts: the "PRONE" Study (PRONE) was conducted in non-intubated hospitalized patients with coronavirus disease 2019 (COVID-19) pneumonia as defined by respiratory rate ≥ 20/min or an oxyhemoglobin saturation (SpO2) ≤ 93% without supplemental oxygen [1]. The PRONE trial was designed to investigate the effects of prone positioning on need for escalation in respiratory support, as defined by need for transition to a higher acuity level of care, increased fraction of inspired oxygen (FiO2), or the initiation of invasive mechanical ventilation. Secondary objectives were to assess the duration of effect of prone positioning on respiratory parameters such as respiratory rate and SpO2, as well as other outcomes such as time to discharge or transition in level of care.
Project description:IntroductionCurrent treatment with vasodilators for pulmonary hypertension associated with respiratory diseases is limited by their inhibitory effect on hypoxic pulmonary vasoconstriction (HPV) and uncoupling effects on ventilation-perfusion (V'/Q'). Hypoxia is also a well-known modulator of the nitric oxide (NO) pathway, and may therefore differentially affect the responses to phosphodiesterase 5 (PDE5) inhibitors and soluble guanylyl cyclase (sGC) stimulators. So far, the effects of the sGC stimulator riociguat on HPV have been poorly characterized.Materials and methodsContraction was recorded in pulmonary arteries (PA) in a wire myograph. Anesthetized rats were catheterized to record PA pressure. Ventilation and perfusion were analyzed by micro-CT-SPECT images in rats with pulmonary fibrosis induced by bleomycin.ResultsThe PDE5 inhibitor sildenafil and the sGC stimulator riociguat similarly inhibited HPV in vitro and in vivo. Riociguat was more effective as vasodilator in isolated rat and human PA than sildenafil. Riociguat was ≈3-fold more potent under hypoxic conditions and it markedly inhibited HPV in vivo at a dose that barely affected the thromboxane A2 (TXA2) mimetic U46619-induced pressor responses. Pulmonary fibrosis was associated with V'/Q' uncoupling and riociguat did not affect the V'/Q' ratio.ConclusionPDE5 inhibitors and sGC stimulators show a different vasodilator profile. Riociguat was highly effective and potentiated by hypoxia in rat and human PA. In vivo, riociguat preferentially inhibited hypoxic than non-hypoxic vasoconstriction. However, it did not worsen V'/Q' coupling in a rat model of pulmonary fibrosis.