Effects of CPAP and FiO2 on respiratory effort and lung stress in early COVID-19 pneumonia: a randomized, crossover study.

BACKGROUND: in COVID-19 acute respiratory failure, the effects of CPAP and FiO2 on respiratory effort and lung stress are unclear. We hypothesize that, in the compliant lungs of early Sars-CoV-2 pneumonia, the application of positive pressure through Helmet-CPAP may not decrease respiratory effort, and rather worsen lung stress and oxygenation when compared to higher FiO2 delivered via oxygen masks. METHODS: In this single-center (S.Luigi Gonzaga University-Hospital, Turin, Italy), randomized, crossover study, we included patients receiving Helmet-CPAP for early (< 48 h) COVID-19 pneumonia without additional cardiac or respiratory disease. Healthy subjects were included as controls. Participants were equipped with an esophageal catheter, a non-invasive cardiac output monitor, and an arterial catheter. The protocol consisted of a random sequence of non-rebreather mask (NRB), Helmet-CPAP (with variable positive pressure and FiO2) and Venturi mask (FiO2 0.5), each delivered for 20 min. Study outcomes were changes in respiratory effort (esophageal swing), total lung stress (dynamic + static transpulmonary pressure), gas-exchange and hemodynamics. RESULTS: We enrolled 28 COVID-19 patients and 7 healthy controls. In all patients, respiratory effort increased from NRB to Helmet-CPAP (5.0 ± 3.7 vs 8.3 ± 3.9 cmH2O, p < 0.01). However, Helmet's pressure decreased by a comparable amount during inspiration (- 3.1 ± 1.0 cmH2O, p = 0.16), therefore dynamic stress remained stable (p = 0.97). Changes in static and total lung stress from NRB to Helmet-CPAP were overall not significant (p = 0.07 and p = 0.09, respectively), but showed high interpatient variability, ranging from - 4.5 to + 6.1 cmH2O, and from - 5.8 to + 5.7 cmH2O, respectively. All findings were confirmed in healthy subjects, except for an increase in dynamic stress (p < 0.01). PaO2 decreased from NRB to Helmet-CPAP with FiO2 0.5 (107 ± 55 vs 86 ± 30 mmHg, p < 0.01), irrespective of positive pressure levels (p = 0.64). Conversely, with Helmet's FiO2 0.9, PaO2 increased (p < 0.01), but oxygen delivery remained stable (p = 0.48) as cardiac output decreased (p = 0.02). When PaO2 fell below 60 mmHg with VM, respiratory effort increased proportionally (p < 0.01, r = 0.81). CONCLUSIONS: In early COVID-19 pneumonia, Helmet-CPAP increases respiratory effort without altering dynamic stress, while the effects upon static and total stress are variable, requiring individual assessment. Oxygen masks with higher FiO2 provide better oxygenation with lower respiratory effort. Trial registration Retrospectively registered (13-May-2021): clinicaltrials.gov (NCT04885517), https://clinicaltrials.gov/ct2/show/NCT04885517 .

End-Tidal to Arterial Pco2 Ratio as Guide to Weaning from Venovenous Extracorporeal Membrane Oxygenation.

Rationale: Weaning from venovenous extracorporeal membrane oxygenation (VV-ECMO) is based on oxygenation and not on carbon dioxide elimination. Objectives: To predict readiness to wean from VV-ECMO. Methods: In this multicenter study of mechanically ventilated adults with severe acute respiratory distress syndrome receiving VV-ECMO, we investigated a variable based on CO2 elimination. The study included a prospective interventional study of a physiological cohort (n = 26) and a retrospective clinical cohort (n = 638). Measurements and Main Results: Weaning failure in the clinical and physiological cohorts were 37% and 42%, respectively. The main cause of failure in the physiological cohort was high inspiratory effort or respiratory rate. All patients exhaled similar amounts of CO2, but in patients who failed the weaning trial, [Formula: see text]e was higher to maintain the PaCO2 unchanged. The effort to eliminate one unit-volume of CO2, was double in patients who failed (68.9 [42.4-123] vs. 39 [20.1-57] cm H2O/[L/min]; P = 0.007), owing to the higher physiological Vd (68 [58.73] % vs. 54 [41.64] %; P = 0.012). End-tidal partial carbon dioxide pressure (PetCO2)/PaCO2 ratio was a clinical variable strongly associated with weaning outcome at baseline, with area under the receiver operating characteristic curve of 0.87 (95% confidence interval [CI], 0.71-1). Similarly, the PetCO2/PaCO2 ratio was associated with weaning outcome in the clinical cohort both before the weaning trial (odds ratio, 4.14; 95% CI, 1.32-12.2; P = 0.015) and at a sweep gas flow of zero (odds ratio, 13.1; 95% CI, 4-44.4; P < 0.001). Conclusions: The primary reason for weaning failure from VV-ECMO is high effort to eliminate CO2. A higher PetCO2/PaCO2 ratio was associated with greater likelihood of weaning from VV-ECMO.

Mobilizing Carbon Dioxide Stores. An Experimental Study.

Rationale: Understanding the physiology of CO2 stores mobilization is a prerequisite for intermittent extracorporeal CO2 removal (ECCO2R) in patients with chronic hypercapnia.Objectives: To describe the dynamics of CO2 stores.Methods: Fifteen pigs (61.7 ± 4.3 kg) were randomized to 48 hours of hyperventilation (group "Hyper," n = 4); 48 hours of hypoventilation (group "Hypo," n = 4); 24 hours of hypoventilation plus 24 hours of normoventilation (group "Hypo-Baseline," n = 4); or 24 hours of hypoventilation plus 24 hours of hypoventilation plus ECCO2R (group "Hypo-ECCO2R," n = 3). Forty-eight hours after randomization, the current [Formula: see text]e was reduced by 50% in every pig.Measurements and Main Results: We evaluated [Formula: see text]co2, [Formula: see text]o2, and metabolic [Formula: see text]co2 ([Formula: see text]o2 times the metabolic respiratory quotient). Changes in the CO2 stores were calculated as [Formula: see text]co2 - metabolic V̇co2. After 48 hours, the CO2 stores decreased by 0.77 ± 0.17 l kg-1 in group Hyper and increased by 0.32 ± 0.27 l kg-1 in group Hypo (P = 0.030). In group Hypo-Baseline, they increased by 0.08 ± 0.19 l kg-1, whereas in group Hypo-ECCO2R, they decreased by 0.32 ± 0.24 l kg-1 (P = 0.197). In the second 24-hour period, in groups Hypo-Baseline and Hypo-ECCO2R, the CO2 stores decreased by 0.15 ± 0.09 l kg-1 and 0.51 ± 0.06 l kg-1, respectively (P = 0.002). At the end of the experiment, the 50% reduction of [Formula: see text]e caused a PaCO2 rise of 9.3 ± 1.1, 32.0 ± 5.0, 16.9 ± 1.2, and 11.7 ± 2.0 mm Hg h-1 in groups Hyper, Hypo, Hypo-Baseline, and Hypo-ECCO2R, respectively (P < 0.001). The PaCO2 rise was inversely related to the previous CO2 stores mobilization (P < 0.001).Conclusions: CO2 from body stores can be mobilized over 48 hours without reaching a steady state. This provides a physiological rationale for intermittent ECCO2R in patients with chronic hypercapnia.

Pentraxin-3, Troponin T, N-Terminal Pro-B-Type Natriuretic Peptide in Septic Patients.

OBJECTIVE: To investigate the behavior of pentraxin-3 (PTX3), troponin T (hsTnT), N-terminal pro-B type Natriuretic Peptide (NT-proBNP) in sepsis and their relationships with sepsis severity and oxygen transport/utilization impairment. DESIGN: Retrospective analysis of PTX3, hsTnT, NT-proBNP levels at day 1, 2, and 7 after admission in the intensive care unit in a subset of the Albumin Italian Outcome Sepsis database. SETTING: Forty Italian intensive care units. PATIENTS: Nine hundred fifty-eight septic patients enrolled in the randomized clinical trial comparing albumin replacement plus crystalloids and crystalloids alone. INTERVENTIONS: The patients were divided into sextiles of lactate (marker of severity), ScvO2 (marker of oxygen transport), and fluid balance (marker of therapeutic strategy). MEASUREMENTS AND MAIN RESULTS: PTX3 and hsTnT were remarkably similar in the two treatment arms, while NT-proBNP was almost double in the albumin treatment group. However, as the distribution of all these biomarkers was similar between control and treatment arms, for the sake of clarity, we analyzed the patients as a single cohort. PTX3 (71.8 [32.9-186.3] ng/mL), hsTnT (50.4 [21.6-133.6] ng/L), and NT-proBNP (4,393 [1,313-13,837] ng/L) were abnormally elevated in 100%, 84.5%, 93.4% of the 953 patients and all decreased from day 1 to day 7. PTX3 monotonically increased with increasing lactate levels. The hsTnT levels were significantly higher when ScvO2 levels were abnormally low (< 70%), suggesting impaired oxygen transport compared with higher ScvO2 levels, suggesting impaired oxygen utilization. NT-proBNP was higher with higher lactate and fluid balance. At ScvO2 levels < 70%, the NT-proBNP was higher than at higher ScvO2 levels. However, even with higher ScvO2, the NT-proBNP was remarkably elevated, suggesting volume expansion. Increased level of NT-proBNP showed the strongest association with 90-day mortality. CONCLUSIONS: The selected biomarkers seem related to different mechanisms during sepsis: PTX3 to sepsis severity, hsTnT to impaired oxygen transport, NT-proBNP to sepsis severity, oxygen transport, and aggressive fluid strategy.

Does Iso-mechanical Power Lead to Iso-lung Damage?: An Experimental Study in a Porcine Model.

BACKGROUND: Excessive tidal volume, respiratory rate, and positive end-expiratory pressure (PEEP) are all potential causes of ventilator-induced lung injury, and all contribute to a single variable: the mechanical power. The authors aimed to determine whether high tidal volume or high respiratory rate or high PEEP at iso-mechanical power produce similar or different ventilator-induced lung injury. METHODS: Three ventilatory strategies-high tidal volume (twice baseline functional residual capacity), high respiratory rate (40 bpm), and high PEEP (25 cm H2O)-were each applied at two levels of mechanical power (15 and 30 J/min) for 48 h in six groups of seven healthy female piglets (weight: 24.2 ± 2.0 kg, mean ± SD). RESULTS: At iso-mechanical power, the high tidal volume groups immediately and sharply increased plateau, driving pressure, stress, and strain, which all further deteriorated with time. In high respiratory rate groups, they changed minimally at the beginning, but steadily increased during the 48 h. In contrast, after a sudden huge increase, they decreased with time in the high PEEP groups. End-experiment specific lung elastance was 6.5 ± 1.7 cm H2O in high tidal volume groups, 10.1 ± 3.9 cm H2O in high respiratory rate groups, and 4.5 ± 0.9 cm H2O in high PEEP groups. Functional residual capacity decreased and extravascular lung water increased similarly in these three categories. Lung weight, wet-to-dry ratio, and histologic scores were similar, regardless of ventilatory strategies and power levels. However, the alveolar edema score was higher in the low power groups. High PEEP had the greatest impact on hemodynamics, leading to increased need for fluids. Adverse events (early mortality and pneumothorax) also occurred more frequently in the high PEEP groups. CONCLUSIONS: Different ventilatory strategies, delivered at iso-power, led to similar anatomical lung injury. The different systemic consequences of high PEEP underline that ventilator-induced lung injury must be evaluated in the context of the whole body.

Mechanical power at a glance: a simple surrogate for volume-controlled ventilation.

BACKGROUND: Mechanical power is a summary variable including all the components which can possibly cause VILI (pressures, volume, flow, respiratory rate). Since the complexity of its mathematical computation is one of the major factors that delay its clinical use, we propose here a simple and easy to remember equation to estimate mechanical power under volume-controlled ventilation: [Formula: see text] where the mechanical power is expressed in Joules/minute, the minute ventilation (VE) in liters/minute, the inspiratory flow (F) in liters/minute, and peak pressure and positive end-expiratory pressure (PEEP) in centimeter of water. All the components of this equation are continuously displayed by any ventilator under volume-controlled ventilation without the need for clinician intervention. To test the accuracy of this new equation, we compared it with the reference formula of mechanical power that we proposed for volume-controlled ventilation in the past. The comparisons were made in a cohort of mechanically ventilated pigs (485 observations) and in a cohort of ICU patients (265 observations). RESULTS: Both in pigs and in ICU patients, the correlation between our equation and the reference one was close to the identity. Indeed, the R2 ranged from 0.97 to 0.99 and the Bland-Altman showed small biases (ranging from + 0.35 to - 0.53 J/min) and proportional errors (ranging from + 0.02 to - 0.05). CONCLUSIONS: Our new equation of mechanical power for volume-controlled ventilation represents a simple and accurate alternative to the more complex ones available to date. This equation does not need any clinical intervention on the ventilator (such as an inspiratory hold) and could be easily implemented in the software of any ventilator in volume-controlled mode. This would allow the clinician to have an estimation of mechanical power at a simple glance and thus increase the clinical consciousness of this variable which is still far from being used at the bedside. Our equation carries the same limitations of all other formulas of mechanical power, the most important of which, as far as it concerns VILI prevention, are the lack of normalization and its application to the whole respiratory system (including the chest wall) and not only to the lung parenchyma.

Prone Positioning in Acute Respiratory Distress Syndrome.

Prone positioning is nowadays considered as one of the most effective strategies for patients with severe acute respiratory distress syndrome (ARDS). The evolution of the pathophysiological understanding surrounding the prone position closely follows the history of ARDS. At the beginning, the focus of the prone position was the improvement in oxygenation attributed to a perfusion redistribution. However, the mechanisms behind the prone position are more complex. Indeed, the positive effects on oxygenation and CO2 clearance of the prone position are to be ascribed to a more homogeneous inflation-ventilation, to the lung/thoracic shape mismatch, and to the change of chest wall elastance. In the past 20 years, five major trials have tried, starting from different theories, hypotheses, and designs, to demonstrate the effectiveness of the prone position, which finally found its definitive place among the different ARDS supportive therapies.