Short-term effects of small volume saline infusion on acid base equilibrium in critically ill patients.

BACKGROUND: Short-term acid-base effects of 0.9% saline solution infusion are not well described. Aim of this study was to assess the effects of a fluid challenge with 0.9% saline in critically ill patients according to the Stewart's approach, which allows a precise determination of acid base equilibrium. METHODS: In 40 mechanically ventilated critically ill patients, acid-base variables according to Stewart's approach were measured before and after 30 minutes from the infusion of 0.5L of 0.9% saline. Patients were divided in saline responder (fractional sodium excretion increase <0.5) and non-responders, and in patients with (estimated glomerular filtration rate >63 mL/min) and without renal impairment. RESULTS: After saline infusion, plasma sodium concentration did not change (138 [135-141] vs. 138 [135-140] mEq/L, P=0.646), while chloride concentration significantly increased (102 [100-106] vs. 104 [191-106] mEq/L, P=0.003), reducing strong ion difference (37.0 [34.9-38.0] vs. 35.4 [32.7-37.5] mEq/L, P=0.004) without any impact on pH, due to the concomitant albumin dilution. In saline non-responders, the increase of plasma chloride concentration caused a reduction in strong ion difference, while in saline responders both plasma chloride concentration and strong ion difference remained similar. Patients with and without renal impairment presented a similar acid-base response. CONCLUSIONS: The infusion of 0.9% saline reduced strong ion difference by increasing plasma chloride concentration, with no effect on pH due to concomitant albumin dilution. Saline non-responders, characterized by the ability to excrete the sodium excess, were more likely to suffer the acidifying effects of saline infusion, while renal function did not affect the acid-base response to saline infusion.

The evaluation of a non-invasive respiratory monitor in ards patients in supine and prone position.

PURPOSE: The Prone positioning in addition to non invasive respiratory support is commonly used in patients with acute respiratory failure. The aim of this study was to assess the accuracy of an impedance-based non-invasive respiratory volume monitor (RVM) in supine and in prone position. METHODS: In sedated, paralyzed and mechanically ventilated patients in volume-controlled mode with acute respiratory distress syndrome scheduled for prone positioning it was measured and compared non-invasively tidal volume and respiratory rate provided by the RVM in supine and, subsequently, in prone position, by maintaining unchanged the ventilatory setting. RESULTS: Forty patients were enrolled. No significant difference was found between measurements in supine and in prone position either for tidal volume (p = 0.795; p = 0.302) nor for respiratory rate (p = 0.181; p = 0.604). Comparing supine vs. prone position, the bias and limits of agreements for respiratory rate were 0.12 bpm (-1.4 to 1.6) and 20 mL (-80 to 120) for tidal volume. CONCLUSIONS: The RVM is accurate in assessing tidal volume and respiratory rate in prone compared to supine position. Therefore, the RVM could be applied in non-intubated patients with acute respiratory failure receiving prone positioning to monitor respiratory function.

Determinants of acute kidney injury during high-power mechanical ventilation: secondary analysis from experimental data.

BACKGROUND: The individual components of mechanical ventilation may have distinct effects on kidney perfusion and on the risk of developing acute kidney injury; we aimed to explore ventilatory predictors of acute kidney failure and the hemodynamic changes consequent to experimental high-power mechanical ventilation. METHODS: Secondary analysis of two animal studies focused on the outcomes of different mechanical power settings, including 78 pigs mechanically ventilated with high mechanical power for 48 h. The animals were categorized in four groups in accordance with the RIFLE criteria for acute kidney injury (AKI), using the end-experimental creatinine: (1) NO AKI: no increase in creatinine; (2) RIFLE 1-Risk: increase of creatinine of > 50%; (3) RIFLE 2-Injury: two-fold increase of creatinine; (4) RIFLE 3-Failure: three-fold increase of creatinine; RESULTS: The main ventilatory parameter associated with AKI was the positive end-expiratory pressure (PEEP) component of mechanical power. At 30 min from the initiation of high mechanical power ventilation, the heart rate and the pulmonary artery pressure progressively increased from group NO AKI to group RIFLE 3. At 48 h, the hemodynamic variables associated with AKI were the heart rate, cardiac output, mean perfusion pressure (the difference between mean arterial and central venous pressures) and central venous pressure. Linear regression and receiving operator characteristic analyses showed that PEEP-induced changes in mean perfusion pressure (mainly due to an increase in CVP) had the strongest association with AKI. CONCLUSIONS: In an experimental setting of ventilation with high mechanical power, higher PEEP had the strongest association with AKI. The most likely physiological determinant of AKI was an increase of pleural pressure and CVP with reduced mean perfusion pressure. These changes resulted from PEEP per se and from increase in fluid administration to compensate for hemodynamic impairment consequent to high PEEP.

Impact of mechanical power and positive end expiratory pressure on central vs. mixed oxygen and carbon dioxide related variables in a population of female piglets.

INTRODUCTION: The use of the pulmonary artery catheter has decreased overtime; central venous blood gases are generally used in place of mixed venous samples. We want to evaluate the accuracy of oxygen and carbon dioxide related parameters from a central versus a mixed venous sample, and whether this difference is influenced by mechanical ventilation. MATERIALS AND METHODS: We analyzed 78 healthy female piglets ventilated with different mechanical power. RESULTS: There was a significant difference in oxygen-derived parameters between samples taken from the central venous and mixed venous blood (S v ¯ $$ \overline{v} $$ O2 = 74.6%, ScvO2 = 83%, p < 0.0001). Conversely, CO2-related parameters were similar, with strong correlation. Ventilation with higher mechanical power and PEEP increased the difference between oxygen saturations, (Δ[ScvO2-S v ¯ $$ \overline{v} $$ O2 ] = 7.22% vs. 10.0% respectively in the low and high MP groups, p = 0.020); carbon dioxide-related parameters remained unchanged (p = 0.344). CONCLUSIONS: The venous oxygen saturation (central or mixed) may be influenced by the effects of mechanical ventilation. Therefore, central venous data should be interpreted with more caution when using higher mechanical power. On the contrary, carbon dioxide-derived parameters are more stable and similar between the two sampling sites, independently of mechanical power or positive end expiratory pressures.

Estimation of normal lung weight index in healthy female domestic pigs.

INTRODUCTION: Lung weight is an important study endpoint to assess lung edema in porcine experiments on acute respiratory distress syndrome and ventilatory induced lung injury. Evidence on the relationship between lung-body weight relationship is lacking in the literature. The aim of this work is to provide a reference equation between normal lung and body weight in female domestic piglets. MATERIALS AND METHODS: 177 healthy female domestic piglets from previous studies were included in the analysis. Lung weight was assessed either via a CT-scan before any experimental injury or with a scale after autopsy. The animals were randomly divided in a training (n = 141) and a validation population (n = 36). The relation between body weight and lung weight index (lung weight/body weight, g/kg) was described by an exponential function on the training population. The equation was tested on the validation population. A Bland-Altman analysis was performed to compare the lung weight index in the validation population and its theoretical value calculated with the reference equation. RESULTS: A good fit was found between the validation population and the exponential equation extracted from the training population (RMSE = 0.060). The equation to determine lung weight index from body weight was: [Formula: see text] At the Bland and Altman analyses, the mean bias between the real and the expected lung weight index was - 0.26 g/kg (95% CI - 0.96-0.43), upper LOA 3.80 g/kg [95% CI 2.59-5.01], lower LOA - 4.33 g/kg [95% CI = - 5.54-(- 3.12)]. CONCLUSIONS: This exponential function might be a valuable tool to assess lung edema in experiments involving 16-50 kg female domestic piglets. The error that can be made due to the 95% confidence intervals of the formula is smaller than the one made considering the lung to body weight as a linear relationship.

Early time-course of respiratory mechanics, mechanical power and gas exchange in ARDS patients.

PURPOSE: To describe the clinical course of ARDS during the first three days of mechanical ventilation, to compare ventilatory setting, respiratory mechanics and gas exchange variables collected during the first three days of mechanical ventilation between patients who survived and died during intensive care unit (ICU) stay and to investigate the variables associated with mortality at ICU admission and throughout the first three days of mechanical ventilation. MATERIALS AND METHODS: Prospective observational study. Mechanically ventilated ARDS patients were studied at ICU admission and for the following three days. Univariate logistic regression models were performed for PaO2/FiO2 ratio, driving pressure and alveolar dead space fraction and for mechanical power and mechanical power ratio. RESULTS: Mechanical power ratio was higher in non survivors at ICU admission and over time; PaO2/FiO2 ratio was higher in survivors with a similar behavior over time in the two groups while alveolar dead space fraction was similar at ICU admission and over time between groups. Mechanical power ratio was the only physiological variable which remained consistently associated with ICU mortality throughout the study. CONCLUSIONS: The alteration in oxygenation, dead space, and mechanical power ratio should be assessed not at intensive care admission, but during the first days of mechanical ventilation to better predict outcome.

Machine learning predicts lung recruitment in acute respiratory distress syndrome using single lung CT scan.

BACKGROUND: To develop and validate classifier models that could be used to identify patients with a high percentage of potentially recruitable lung from readily available clinical data and from single CT scan quantitative analysis at intensive care unit admission. 221 retrospectively enrolled mechanically ventilated, sedated and paralyzed patients with acute respiratory distress syndrome (ARDS) underwent a PEEP trial at 5 and 15 cmH2O of PEEP and two lung CT scans performed at 5 and 45 cmH2O of airway pressure. Lung recruitability was defined at first as percent change in not aerated tissue between 5 and 45 cmH2O (radiologically defined; recruiters: Δ45-5non-aerated tissue > 15%) and secondly as change in PaO2 between 5 and 15 cmH2O (gas exchange-defined; recruiters: Δ15-5PaO2 > 24 mmHg). Four machine learning (ML) algorithms were evaluated as classifiers of radiologically defined and gas exchange-defined lung recruiters using different models including different variables, separately or combined, of lung mechanics, gas exchange and CT data. RESULTS: ML algorithms based on CT scan data at 5 cmH2O classified radiologically defined lung recruiters with similar AUC as ML based on the combination of lung mechanics, gas exchange and CT data. ML algorithm based on CT scan data classified gas exchange-defined lung recruiters with the highest AUC. CONCLUSIONS: ML based on a single CT data at 5 cmH2O represented an easy-to-apply tool to classify ARDS patients in recruiters and non-recruiters according to both radiologically defined and gas exchange-defined lung recruitment within the first 48 h from the start of mechanical ventilation.

Differences in clinical characteristics and quantitative lung CT features between vaccinated and not vaccinated hospitalized COVID-19 patients in Italy.

BACKGROUND: To evaluate the differences in the clinical characteristics and severity of lung impairment, assessed by quantitative lung CT scan, between vaccinated and non-vaccinated hospitalized patients with COVID-19; and to identify the variables with best prognostic prediction according to SARS-CoV-2 vaccination status. We recorded clinical, laboratory and quantitative lung CT scan data in 684 consecutive patients [580 (84.8%) vaccinated, and 104 (15.2%) non-vaccinated], admitted between January and December 2021. RESULTS: Vaccinated patients were significantly older 78 [69-84] vs 67 [53-79] years and with more comorbidities. Vaccinated and non-vaccinated patients had similar PaO2/FiO2 (300 [252-342] vs 307 [247-357] mmHg; respiratory rate 22 [8-26] vs 19 [18-26] bpm); total lung weight (918 [780-1069] vs 954 [802-1149] g), lung gas volume (2579 [1801-3628] vs 2370 [1675-3289] mL) and non-aerated tissue fraction (10 [7.3-16.0] vs 8.5 [6.0-14.1] %). The overall crude hospital mortality was similar between the vaccinated and non-vaccinated group (23.1% vs 21.2%). However, Cox regression analysis, adjusted for age, ethnicity, age unadjusted Charlson Comorbidity Index and calendar month of admission, showed a 40% reduction in hospital mortality in the vaccinated patients (HRadj = 0.60, 95%CI 0.38-0.95). CONCLUSIONS: Hospitalized vaccinated patients with COVID-19, although older and with more comorbidities, presented a similar impairment in gas exchange and lung CT scan compared to non-vaccinated patients, but were at a lower risk of mortality.

High- versus Low-Flow Extracorporeal Respiratory Support in Experimental Hypoxemic Acute Lung Injury.

Rationale: In the EOLIA (ECMO to Rescue Lung Injury in Severe ARDS) trial, oxygenation was similar between intervention and conventional groups, whereas [Formula: see text]e was reduced in the intervention group. Comparable reductions in ventilation intensity are theoretically possible with low-flow extracorporeal CO2 removal (ECCO2R), provided oxygenation remains acceptable. Objectives: To compare the effects of ECCO2R and extracorporeal membrane oxygenation (ECMO) on gas exchange, respiratory mechanics, and hemodynamics in animal models of pulmonary (intratracheal hydrochloric acid) and extrapulmonary (intravenous oleic acid) lung injury. Methods: Twenty-four pigs with moderate to severe hypoxemia (PaO2:FiO2 ⩽ 150 mm Hg) were randomized to ECMO (blood flow 50-60 ml/kg/min), ECCO2R (0.4 L/min), or mechanical ventilation alone. Measurements and Main Results: [Formula: see text]o2, [Formula: see text]co2, gas exchange, hemodynamics, and respiratory mechanics were measured and are presented as 24-hour averages. Oleic acid versus hydrochloric acid showed higher extravascular lung water (1,424 ± 419 vs. 574 ± 195 ml; P < 0.001), worse oxygenation (PaO2:FiO2 = 125 ± 14 vs. 151 ± 11 mm Hg; P < 0.001), but better respiratory mechanics (plateau pressure 27 ± 4 vs. 30 ± 3 cm H2O; P = 0.017). Both models led to acute severe pulmonary hypertension. In both models, ECMO (3.7 ± 0.5 L/min), compared with ECCO2R (0.4 L/min), increased mixed venous oxygen saturation and oxygenation, and improved hemodynamics (cardiac output = 6.0 ± 1.4 vs. 5.2 ± 1.4 L/min; P = 0.003). [Formula: see text]o2 and [Formula: see text]co2, irrespective of lung injury model, were lower during ECMO, resulting in lower PaCO2 and [Formula: see text]e but worse respiratory elastance compared with ECCO2R (64 ± 27 vs. 40 ± 8 cm H2O/L; P < 0.001). Conclusions: ECMO was associated with better oxygenation, lower [Formula: see text]o2, and better hemodynamics. ECCO2R may offer a potential alternative to ECMO, but there are concerns regarding its effects on hemodynamics and pulmonary hypertension.

Mechanical Power Ratio and Respiratory Treatment Escalation in COVID-19 Pneumonia: A Secondary Analysis of a Prospectively Enrolled Cohort.

BACKGROUND: Under the hypothesis that mechanical power ratio could identify the spontaneously breathing patients with a higher risk of respiratory failure, this study assessed lung mechanics in nonintubated patients with COVID-19 pneumonia, aiming to (1) describe their characteristics; (2) compare lung mechanics between patients who received respiratory treatment escalation and those who did not; and (3) identify variables associated with the need for respiratory treatment escalation. METHODS: Secondary analysis of prospectively enrolled cohort involving 111 consecutive spontaneously breathing adults receiving continuous positive airway pressure, enrolled from September 2020 to December 2021. Lung mechanics and other previously reported predictive indices were calculated, as well as a novel variable: the mechanical power ratio (the ratio between the actual and the expected baseline mechanical power). Patients were grouped according to the outcome: (1) no-treatment escalation (patient supported in continuous positive airway pressure until improvement) and (2) treatment escalation (escalation of the respiratory support to noninvasive or invasive mechanical ventilation), and the association between lung mechanics/predictive scores and outcome was assessed. RESULTS: At day 1, patients undergoing treatment escalation had spontaneous tidal volume similar to those of patients who did not (7.1 ± 1.9 vs. 7.1 ± 1.4 ml/kgIBW; P = 0.990). In contrast, they showed higher respiratory rate (20 ± 5 vs. 18 ± 5 breaths/min; P = 0.028), minute ventilation (9.2 ± 3.0 vs. 7.9 ± 2.4 l/min; P = 0.011), tidal pleural pressure (8.1 ± 3.7 vs. 6.0 ± 3.1 cm H2O; P = 0.003), mechanical power ratio (2.4 ± 1.4 vs. 1.7 ± 1.5; P = 0.042), and lower partial pressure of alveolar oxygen/fractional inspired oxygen tension (174 ± 64 vs. 220 ± 95; P = 0.007). The mechanical power (area under the curve, 0.738; 95% CI, 0.636 to 0.839] P < 0.001), the mechanical power ratio (area under the curve, 0.734; 95% CI, 0.625 to 0.844; P < 0.001), and the pressure-rate index (area under the curve, 0.733; 95% CI, 0.631 to 0.835; P < 0.001) showed the highest areas under the curve. CONCLUSIONS: In this COVID-19 cohort, tidal volume was similar in patients undergoing treatment escalation and in patients who did not; mechanical power, its ratio, and pressure-rate index were the variables presenting the highest association with the clinical outcome.

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.

Long term feasibility of ultraprotective lung ventilation with low-flow extracorporeal carbon dioxide removal in ARDS patients.

PURPOSE: To explore the feasibility of long-term application of ultraprotective ventilation with low flow ECCO2R support in moderate-severe ARDS patients and the reduction of mechanical power (MP) compared to lung protective ventilation. MATERIAL AND METHODS: ARDS patients with PaO2/FiO2 < 200, PEEP of 10 cmH2O, tidal volume 6 ml/Kg of predicted body weight (PBW), plateau pressure > 24 cmH2O, MP > 17 J/min were prospectively enrolled. After 2 h tidal volume was reduced to 4-5 ml/kg, respiratory rate (RR) and PEEP were changed to maintain similar minute ventilation and mean airway pressure (MAP) to those obtained at baseline. After 2 h, ECCO2R support was started, RR was decreased and PEEP was increased to maintain similar PaCO2 and MAP, respectively. RESULTS: The only reduction of tidal volume with the increase in RR did not decrease MP. The application of low flow ECCO2R support allowed a reduction of RR from 25 [24-30] to 11 [9-14] bpm and MP from 18 [13-23] to 8 [7-11] J/min. During the following 5 days no changes in mechanics variables and gas exchange occurred. CONCLUSIONS: The application of low flow ECCO2R support with ultraprotective ventilation was feasible minimizing the MP without deterioration in oxygenation in ARDS patients.

Acid-Base Disorders in COVID-19 Patients with Acute Respiratory Distress Syndrome.

Our aim was to investigate the distribution of acid-base disorders in patients with COVID-19 ARDS using both the Henderson-Hasselbalch and Stewart's approach and to explore if hypoxemia can influence acid-base disorders. COVID-19 ARDS patients, within the first 48 h of the need for a non-invasive respiratory support, were retrospectively enrolled. Respiratory support was provided by helmet continuous positive airway pressure (CPAP) or by non-invasive ventilation. One hundred and four patients were enrolled, 84% treated with CPAP and 16% with non-invasive ventilation. Using the Henderson-Hasselbalch approach, 40% and 32% of patients presented respiratory and metabolic alkalosis, respectively; 13% did not present acid-base disorders. Using Stewart's approach, 43% and 33% had a respiratory and metabolic alkalosis, respectively; 12% of patients had a mixed disorder characterized by normal pH with a lower SID. The severe hypoxemic and moderate hypoxemic group presented similar frequencies of respiratory and metabolic alkalosis. The most frequent acid-base disorders were respiratory and metabolic alkalosis using both the Henderson-Hasselbalch and Stewart's approach. Stewart's approach detected mixed disorders with a normal pH probably generated by the combined effect of strong ions and weak acids. The impairment of oxygenation did not affect acid-base disorders.

Putative Role of the Lung-Brain Axis in the Pathogenesis of COVID-19-Associated Respiratory Failure: A Systematic Review.

The emergence of SARS-CoV-2 and its related disease caused by coronavirus (COVID-19) has posed a huge threat to the global population, with millions of deaths and the creation of enormous social and healthcare pressure. Several studies have shown that besides respiratory illness, other organs may be damaged as well, including the heart, kidneys, and brain. Current evidence reports a high frequency of neurological manifestations in COVID-19, with significant prognostic implications. Importantly, emerging literature is showing that the virus may spread to the central nervous system through neuronal routes, hitting the brainstem and cardiorespiratory centers, potentially exacerbating the respiratory illness. In this systematic review, we searched public databases for all available evidence and discuss current clinical and pre-clinical data on the relationship between the lung and brain during COVID-19. Acknowledging the involvement of these primordial brain areas in the pathogenesis of the disease may fuel research on the topic and allow the development of new therapeutic strategies.

Positive end-expiratory pressure in COVID-19 acute respiratory distress syndrome: the heterogeneous effects.

BACKGROUND: We hypothesized that as CARDS may present different pathophysiological features than classic ARDS, the application of high levels of end-expiratory pressure is questionable. Our first aim was to investigate the effects of 5-15 cmH2O of PEEP on partitioned respiratory mechanics, gas exchange and dead space; secondly, we investigated whether respiratory system compliance and severity of hypoxemia could affect the response to PEEP on partitioned respiratory mechanics, gas exchange and dead space, dividing the population according to the median value of respiratory system compliance and oxygenation. Thirdly, we explored the effects of an additional PEEP selected according to the Empirical PEEP-FiO2 table of the EPVent-2 study on partitioned respiratory mechanics and gas exchange in a subgroup of patients. METHODS: Sixty-one paralyzed mechanically ventilated patients with a confirmed diagnosis of SARS-CoV-2 were enrolled (age 60 [54-67] years, PaO2/FiO2 113 [79-158] mmHg and PEEP 10 [10-10] cmH2O). Keeping constant tidal volume, respiratory rate and oxygen fraction, two PEEP levels (5 and 15 cmH2O) were selected. In a subgroup of patients an additional PEEP level was applied according to an Empirical PEEP-FiO2 table (empirical PEEP). At each PEEP level gas exchange, partitioned lung mechanics and hemodynamic were collected. RESULTS: At 15 cmH2O of PEEP the lung elastance, lung stress and mechanical power were higher compared to 5 cmH2O. The PaO2/FiO2, arterial carbon dioxide and ventilatory ratio increased at 15 cmH2O of PEEP. The arterial-venous oxygen difference and central venous saturation were higher at 15 cmH2O of PEEP. Both the mechanics and gas exchange variables significantly increased although with high heterogeneity. By increasing the PEEP from 5 to 15 cmH2O, the changes in partitioned respiratory mechanics and mechanical power were not related to hypoxemia or respiratory compliance. The empirical PEEP was 18 ± 1 cmH2O. The empirical PEEP significantly increased the PaO2/FiO2 but also driving pressure, lung elastance, lung stress and mechanical power compared to 15 cmH2O of PEEP. CONCLUSIONS: In COVID-19 ARDS during the early phase the effects of raising PEEP are highly variable and cannot easily be predicted by respiratory system characteristics, because of the heterogeneity of the disease.