Impact of respiratory cycle during mechanical ventilation on beat-to-beat right ventricle stroke volume estimation by pulmonary artery pulse wave analysis.

BACKGROUND: The same principle behind pulse wave analysis can be applied on the pulmonary artery (PA) pressure waveform to estimate right ventricle stroke volume (RVSV). However, the PA pressure waveform might be influenced by the direct transmission of the intrathoracic pressure changes throughout the respiratory cycle caused by mechanical ventilation (MV), potentially impacting the reliability of PA pulse wave analysis (PAPWA). We assessed a new method that minimizes the direct effect of the MV on continuous PA pressure measurements and enhances the reliability of PAPWA in tracking beat-to-beat RVSV. METHODS: Continuous PA pressure and flow were simultaneously measured for 2-3 min in 5 pigs using a high-fidelity micro-tip catheter and a transonic flow sensor around the PA trunk, both pre and post an experimental ARDS model. RVSV was estimated by PAPWA indexes such as pulse pressure (SVPP), systolic area (SVSystAUC) and standard deviation (SVSD) beat-to-beat from both corrected and non-corrected PA signals. The reference RVSV was derived from the PA flow signal (SVref). RESULTS: The reliability of PAPWA in tracking RVSV on a beat-to-beat basis was enhanced after accounting for the direct impact of intrathoracic pressure changes induced by MV throughout the respiratory cycle. This was evidenced by an increase in the correlation between SVref and RVSV estimated by PAPWA under healthy conditions: rho between SVref and non-corrected SVSD - 0.111 (0.342), corrected SVSD 0.876 (0.130), non-corrected SVSystAUC 0.543 (0.141) and corrected SVSystAUC 0.923 (0.050). Following ARDS, correlations were SVref and non-corrected SVSD - 0.033 (0.262), corrected SVSD 0.839 (0.077), non-corrected SVSystAUC 0.483 (0.114) and corrected SVSystAUC 0.928 (0.026). Correction also led to reduced limits of agreement between SVref and SVSD and SVSystAUC in the two evaluated conditions. CONCLUSIONS: In our experimental model, we confirmed that correcting for mechanical ventilation induced changes during the respiratory cycle improves the performance of PAPWA for beat-to-beat estimation of RVSV compared to uncorrected measurements. This was demonstrated by a better correlation and agreement between the actual SV and the obtained from PAPWA.

Clinical validation of a capnodynamic method for measuring end-expiratory lung volume in critically ill patients.

RATIONALE: End-expiratory lung volume (EELV) is reduced in mechanically ventilated patients, especially in pathologic conditions. The resulting heterogeneous distribution of ventilation increases the risk for ventilation induced lung injury. Clinical measurement of EELV however, remains difficult. OBJECTIVE: Validation of a novel continuous capnodynamic method based on expired carbon dioxide (CO2) kinetics for measuring EELV in mechanically ventilated critically-ill patients. METHODS: Prospective study of mechanically ventilated patients scheduled for a diagnostic computed tomography exploration. Comparisons were made between absolute and corrected EELVCO2 values, the latter accounting for the amount of CO2 dissolved in lung tissue, with the reference EELV measured by computed tomography (EELVCT). Uncorrected and corrected EELVCO2 was compared with total CT volume (density compartments between - 1000 and 0 Hounsfield units (HU) and functional CT volume, including density compartments of - 1000 to - 200HU eliminating regions of increased shunt. We used comparative statistics including correlations and measurement of accuracy and precision by the Bland Altman method. MEASUREMENTS AND MAIN RESULTS: Of the 46 patients included in the final analysis, 25 had a diagnosis of ARDS (24 of which COVID-19). Both EELVCT and EELVCO2 were significantly reduced (39 and 40% respectively) when compared with theoretical values of functional residual capacity (p < 0.0001). Uncorrected EELVCO2 tended to overestimate EELVCT with a correlation r2 0.58; Bias - 285 and limits of agreement (LoA) (+ 513 to - 1083; 95% CI) ml. Agreement improved for the corrected EELVCO2 to a Bias of - 23 and LoA of (+ 763 to - 716; 95% CI) ml. The best agreement of the method was obtained by comparison of corrected EELVCO2 with functional EELVCT with a r2 of 0.59; Bias - 2.75 (+ 755 to - 761; 95% CI) ml. We did not observe major differences in the performance of the method between ARDS (most of them COVID related) and non-ARDS patients. CONCLUSION: In this first validation in critically ill patients, the capnodynamic method provided good estimates of both total and functional EELV. Bias improved after correcting EELVCO2 for extra-alveolar CO2 content when compared with CT estimated volume. If confirmed in further validations EELVCO2 may become an attractive monitoring option for continuously monitor EELV in critically ill mechanically ventilated patients. TRIAL REGISTRATION: clinicaltrials.gov (NCT04045262).

Effect of aggressive vs conservative screening and confirmatory test on time to extubation among patients at low or intermediate risk: a randomized clinical trial.

PURPOSE: This study aimed to determine the best strategy to achieve fast and safe extubation. METHODS: This multicenter trial randomized patients with primary respiratory failure and low-to-intermediate risk for extubation failure with planned high-flow nasal cannula (HFNC) preventive therapy. It included four groups: (1) conservative screening with ratio of partial pressure of arterial oxygen (PaO2) to fraction of inspired oxygen (FiO2) ≥ 150 and positive end-expiratory pressure (PEEP) ≤ 8 cmH2O plus conservative spontaneous breathing trial (SBT) with pressure support 5 cmH2O + PEEP 0 cmH2O); (2) screening with ratio of partial pressure of arterial oxygen (PaO2) to fraction of inspired oxygen (FiO2) ≥ 150 and PEEP ≤ 8 plus aggressive SBT with pressure support 8 + PEEP 5; (3) aggressive screening with PaO2/FiO2 > 180 and PEEP 10 maintained until the SBT with pressure support 8 + PEEP 5; (4) screening with PaO2/FiO2 > 180 and PEEP 10 maintained until the SBT with pressure support 5 + PEEP 0. Primary outcomes were time-to-extubation and simple weaning rate. Secondary outcomes included reintubation within 7 days after extubation. RESULTS: Randomization to the aggressive-aggressive group was discontinued at the interim analysis for safety reasons. Thus, 884 patients who underwent at least 1 SBT were analyzed (conservative-conservative group, n = 256; conservative-aggressive group, n = 267; aggressive-conservative group, n = 261; aggressive-aggressive, n = 100). Median time to extubation was lower in the groups with aggressive screening (p < 0.001). Simple weaning rates were 45.7%, 76.78% (205 patients), 71.65%, and 91% (p < 0.001), respectively. Reintubation rates did not differ significantly (p = 0.431). CONCLUSION: Among patients at low or intermediate risk for extubation failure with planned HFNC, combining aggressive screening with preventive PEEP and a conservative SBT reduced the time to extubation without increasing the reintubation rate.

Effect of postextubation noninvasive ventilation with active humidification vs high-flow nasal cannula on reintubation in patients at very high risk for extubation failure: a randomized trial.

PURPOSE: High-flow nasal cannula (HFNC) oxygen therapy was noninferior to noninvasive ventilation (NIV) for preventing reintubation in a heterogeneous population at high-risk for extubation failure. However, outcomes might differ in certain subgroups of patients. Thus, we aimed to determine whether NIV with active humidification is superior to HFNC in preventing reintubation in patients with ≥ 4 risk factors (very high risk for extubation failure). METHODS: Randomized controlled trial in two intensive care units in Spain (June 2020‒June 2021). Patients ready for planned extubation with ≥ 4 of the following risk factors for reintubation were included: age > 65 years, Acute Physiology and Chronic Health Evaluation II score > 12 on extubation day, body mass index > 30, inadequate secretions management, difficult or prolonged weaning, ≥ 2 comorbidities, acute heart failure indicating mechanical ventilation, moderate-to-severe chronic obstructive pulmonary disease, airway patency problems, prolonged mechanical ventilation, or hypercapnia on finishing the spontaneous breathing trial. Patients were randomized to undergo NIV with active humidification or HFNC for 48 h after extubation. The primary outcome was reintubation rate within 7 days after extubation. Secondary outcomes included postextubation respiratory failure, respiratory infection, sepsis, multiorgan failure, length of stay, mortality, adverse events, and time to reintubation. RESULTS: Of 182 patients (mean age, 60 [standard deviation (SD), 15] years; 117 [64%] men), 92 received NIV and 90 HFNC. Reintubation was required in 21 (23.3%) patients receiving NIV vs 35 (38.8%) of those receiving HFNC (difference -15.5%; 95% confidence interval (CI) -28.3 to -1%). Hospital length of stay was lower in those patients treated with NIV (20 [12‒36.7] days vs 26.5 [15‒45] days, difference 6.5 [95%CI 0.5-21.1]). No additional differences in the other secondary outcomes were observed. CONCLUSIONS: Among adult critically ill patients at very high-risk for extubation failure, NIV with active humidification was superior to HFNC for preventing reintubation.

Benefit with preventive noninvasive ventilation in subgroups of patients at high-risk for reintubation: a post hoc analysis.

BACKGROUND: High-flow nasal cannula (HFNC) was shown to be non-inferior to noninvasive ventilation (NIV) for preventing reintubation in a general population of high-risk patients. However, some subgroups of high-risk patients might benefit more from NIV. We aimed to determine whether the presence of many risk factors or overweight (body mass index (BMI) ≥ 25 kg/m2) patients could have different response to any preventive therapy, NIV or HFNC in terms of reduced reintubation rate. METHODS: Not pre-specified post hoc analysis of a multicentre, randomized, controlled, non-inferiority trial comparing NFNC and NIV to prevent reintubation in patients at risk for reintubation. The original study included patients with at least 1 risk factor for reintubation. RESULTS: Among 604 included in the original study, 148 had a BMI ≥ 25 kg/m2. When adjusting for potential covariates, patients with ≥ 4 risk factors (208 patients) presented a higher risk for reintubation (OR 3.4 [95%CI 2.16-5.35]). Patients with ≥ 4 risk factors presented lower reintubation rates when treated with preventive NIV (23.9% vs 45.7%; P = 0.001). The multivariate analysis of overweight patients, adjusted for covariates, did not present a higher risk for reintubation (OR 1.37 [95%CI 0.82-2.29]). However, those overweight patients presented an increased risk for reintubation when treated with preventive HFNC (OR 2.47 [95%CI 1.18-5.15]). CONCLUSIONS: Patients with ≥ 4 risk factors for reintubation may benefit more from preventive NIV. Based on this result, HFNC may not be the optimal preventive therapy in overweight patients. Specific trials are needed to confirm these results.

Prognostic implications of comorbidity patterns in critically ill COVID-19 patients: A multicenter, observational study.

Background: The clinical heterogeneity of COVID-19 suggests the existence of different phenotypes with prognostic implications. We aimed to analyze comorbidity patterns in critically ill COVID-19 patients and assess their impact on in-hospital outcomes, response to treatment and sequelae. Methods: Multicenter prospective/retrospective observational study in intensive care units of 55 Spanish hospitals. 5866 PCR-confirmed COVID-19 patients had comorbidities recorded at hospital admission; clinical and biological parameters, in-hospital procedures and complications throughout the stay; and, clinical complications, persistent symptoms and sequelae at 3 and 6 months. Findings: Latent class analysis identified 3 phenotypes using training and test subcohorts: low-morbidity (n=3385; 58%), younger and with few comorbidities; high-morbidity (n=2074; 35%), with high comorbid burden; and renal-morbidity (n=407; 7%), with chronic kidney disease (CKD), high comorbidity burden and the worst oxygenation profile. Renal-morbidity and high-morbidity had more in-hospital complications and higher mortality risk than low-morbidity (adjusted HR (95% CI): 1.57 (1.34-1.84) and 1.16 (1.05-1.28), respectively). Corticosteroids, but not tocilizumab, were associated with lower mortality risk (HR (95% CI) 0.76 (0.63-0.93)), especially in renal-morbidity and high-morbidity. Renal-morbidity and high-morbidity showed the worst lung function throughout the follow-up, with renal-morbidity having the highest risk of infectious complications (6%), emergency visits (29%) or hospital readmissions (14%) at 6 months (p<0.01). Interpretation: Comorbidity-based phenotypes were identified and associated with different expression of in-hospital complications, mortality, treatment response, and sequelae, with CKD playing a major role. This could help clinicians in day-to-day decision making including the management of post-discharge COVID-19 sequelae. Funding: ISCIII, UNESPA, CIBERES, FEDER, ESF.

Perioperative Continuous Noninvasive Cardiac Output Monitoring in Cardiac Surgery Patients by a Novel Capnodynamic Method.

OBJECTIVES: To test the clinical performance of a novel continuous noninvasive cardiac output (CO) monitoring based on expired carbon dioxide kinetics in cardiac surgery patients. DESIGN: A prospective feasibility pragmatic clinical study. SETTING: A single-center, large community hospital. PARTICIPANTS: Thirty-two patients undergoing cardiac surgery were studied during the intraoperative (before cardiopulmonary bypass) and postoperative (in the intensive care unit before extubation) periods. INTERVENTIONS: CO was measured simultaneously by the continuous capnodynamic method and by transpulmonary thermodilution during changes in the patient's hemodynamic and/or respiratory conditions. MEASUREMENTS AND MAIN RESULTS: The current recommended comparative statistics for CO measurement methods were analyzed, including bias, precision, and percentage error obtained from Bland-Altman analysis, and concordance between methods obtained from the four-quadrant plot analysis to evaluate the trending ability. Bias ± limits of agreement and percentage error were -0.6 (-1.9 to +0.8; 95% CI of 3.73-5.25) L/min and 31% (n = 147 measurements) for the intraoperative period, -0.8 (-2.4 to +0.9; 95% CI of 3.03-5.21) L/min and 41% (n = 66) for the postoperative period, and -0.6 (-2.1 to +0.8; 95% CI of 3.74-5.00) L/min and 34% (n = 213) for the pooled data. The trending analysis obtained a concordance of 82% (n = 65) for the intraoperative and 71% (n = 24) for the early postoperative periods. Aggregation of both data sets gave a concordance of 79% (n = 89). CONCLUSIONS: The continuous capnodynamic method was reliable and in good agreement with the reference method, and had an accuracy and trending ability good enough to make it a possible future alternative for hemodynamic monitoring in the studied population of elective adult cardiac surgery patients.

Sequential lateral positioning as a new lung recruitment maneuver: an exploratory study in early mechanically ventilated Covid-19 ARDS patients.

BACKGROUND: A sequential change in body position from supine-to-both lateral positions under constant ventilatory settings could be used as a postural recruitment maneuver in case of acute respiratory distress syndrome (ARDS), provided that sufficient positive end-expiratory pressure (PEEP) prevents derecruitment. This study aims to evaluate the feasibility and physiological effects of a sequential postural recruitment maneuver in early mechanically ventilated COVID-19 ARDS patients. METHODS: A cohort of 15 patients receiving lung-protective mechanical ventilation in volume-controlled with PEEP based on recruitability were prospectively enrolled and evaluated in five sequentially applied positions for 30 min each: Supine-baseline; Lateral-1st side; 2nd Supine; Lateral-2nd side; Supine-final. PEEP level was selected using the recruitment-to-inflation ratio (R/I ratio) based on which patients received PEEP 12 cmH2O for R/I ratio ≤ 0.5 or PEEP 15 cmH2O for R/I ratio > 0.5. At the end of each period, we measured respiratory mechanics, arterial blood gases, lung ultrasound aeration, end-expiratory lung impedance (EELI), and regional distribution of ventilation and perfusion using electric impedance tomography (EIT). RESULTS: Comparing supine baseline and final, respiratory compliance (29 ± 9 vs 32 ± 8 mL/cmH2O; p < 0.01) and PaO2/FIO2 ratio (138 ± 36 vs 164 ± 46 mmHg; p < 0.01) increased, while driving pressure (13 ± 2 vs 11 ± 2 cmH2O; p < 0.01) and lung ultrasound consolidation score decreased [5 (4-5) vs 2 (1-4); p < 0.01]. EELI decreased ventrally (218 ± 205 mL; p < 0.01) and increased dorsally (192 ± 475 mL; p = 0.02), while regional compliance increased in both ventral (11.5 ± 0.7 vs 12.9 ± 0.8 mL/cmH2O; p < 0.01) and dorsal regions (17.1 ± 1.8 vs 18.8 ± 1.8 mL/cmH2O; p < 0.01). Dorsal distribution of perfusion increased (64.8 ± 7.3% vs 66.3 ± 7.2%; p = 0.01). CONCLUSIONS: Without increasing airway pressure, a sequential postural recruitment maneuver improves global and regional respiratory mechanics and gas exchange along with a redistribution of EELI from ventral to dorsal lung areas and less consolidation. Trial registration ClinicalTrials.gov, NCT04475068. Registered 17 July 2020, https://clinicaltrials.gov/ct2/show/NCT04475068.

Intraoperative open lung condition and postoperative pulmonary complications. A secondary analysis of iPROVE and iPROVE-O2 trials.

BACKGROUND: The preventive role of an intraoperative recruitment maneuver plus open lung approach (RM + OLA) ventilation on postoperative pulmonary complications (PPC) remains unclear. We aimed at investigating whether an intraoperative open lung condition reduces the risk of developing a composite of PPCs. METHODS: Post hoc analysis of two randomized controlled trials including patients undergoing abdominal surgery. Patients were classified according to the intraoperative lung condition as "open" (OL) or "non-open" (NOL) if PaO2 /FIO2 ratio was ≥ or <400 mmHg, respectively. We used a multivariable logistic regression model that included potential confounders selected with directed acyclic graphs (DAG) using Dagitty software built with variables that were considered clinically relevant based on biological mechanism or evidence from previously published data. PPCs included severe acute respiratory failure, acute respiratory distress syndrome, and pneumonia. RESULTS: A total of 1480 patients were included in the final analysis, with 718 (49%) classified as OL. The rate of severe PPCs during the first seven postoperative days was 6.0% (7.9% in the NOL and 4.4% in the OL group, p = .007). OL was independently associated with a lower risk for severe PPCs during the first 7 and 30 postoperative days [odds ratio of 0.58 (95% CI 0.34-0.99, p = .04) and 0.56 (95% CI 0.34-0.94, p = .03), respectively]. CONCLUSIONS: An intraoperative open lung condition was associated with a reduced risk of developing severe PPCs in intermediate-to-high risk patients undergoing abdominal surgery. TRIAL REGISTRATION: Registered at clinicaltrials.gov NCT02158923 (iPROVE), NCT02776046 (iPROVE-O2).

Positive end-expiratory pressure individualization guided by continuous end-expiratory lung volume monitoring during laparoscopic surgery.

To determine whether end-expiratory lung volume measured with volumetric capnography (EELVCO2) can individualize positive end-expiratory pressure (PEEP) setting during laparoscopic surgery. We studied patients undergoing laparoscopic surgery subjected to Fowler (F-group; n = 20) or Trendelenburg (T-group; n = 20) positions. EELVCO2 was measured at 0° supine (baseline), during capnoperitoneum (CP) at 0° supine, during CP with Fowler (head up + 20°) or Trendelenburg (head down - 30°) positions and after CP back to 0° supine. PEEP was adjusted to preserve baseline EELVCO2 during and after CP. Baseline EELVCO2 was statistically similar to predicted FRC in both groups. At supine and CP, EELVCO2 decreased from baseline values in F-group [median and IQR 2079 (768) to 1545 (725) mL; p = 0.0001] and in T-group [2164 (789) to 1870 (940) mL; p = 0.0001]. Change in body position maintained EELVCO2 unchanged in both groups. PEEP adjustments from 5.6 (1.1) to 10.0 (2.5) cmH2O in the F-group (p = 0.0001) and from 5.6 (0.9) to 10.0 (2.6) cmH2O in T-group (p = 0.0001) were necessary to reach baseline EELVCO2 values. EELVCO2 increased close to baseline with PEEP in the F-group [1984 (600) mL; p = 0.073] and in the T-group [2175 (703) mL; p = 0.167]. After capnoperitoneum and back to 0° supine, PEEP needed to maintain EELVCO2 was similar to baseline PEEP in F-group [5.9 (1.8) cmH2O; p = 0.179] but slightly higher in the T-group [6.5 (2.2) cmH2O; p = 0.006]. Those new PEEP values gave EELVCO2 similar to baseline in the F-group [2039 (980) mL; p = 0.370] and in the T-group [2150 (715) mL; p = 0.881]. Breath-by-breath noninvasive EELVCO2 detected changes in lung volume induced by capnoperitoneum and body position and was useful to individualize the level of PEEP during laparoscopy.Trial registry: Clinicaltrials.gov NCT03693352. Protocol started 1st October 2018.

Unsuccessful and Successful Clinical Trials in Acute Respiratory Distress Syndrome: Addressing Physiology-Based Gaps.

The acute respiratory distress syndrome (ARDS) is a severe form of acute hypoxemic respiratory failure caused by an insult to the alveolar-capillary membrane, resulting in a marked reduction of aerated alveoli, increased vascular permeability and subsequent interstitial and alveolar pulmonary edema, reduced lung compliance, increase of physiological dead space, and hypoxemia. Most ARDS patients improve their systemic oxygenation, as assessed by the ratio between arterial partial pressure of oxygen and inspired oxygen fraction, with conventional intensive care and the application of moderate-to-high levels of positive end-expiratory pressure. However, in some patients hypoxemia persisted because the lungs are markedly injured, remaining unresponsive to increasing the inspiratory fraction of oxygen and positive end-expiratory pressure. For decades, mechanical ventilation was the only standard support technique to provide acceptable oxygenation and carbon dioxide removal. Mechanical ventilation provides time for the specific therapy to reverse the disease-causing lung injury and for the recovery of the respiratory function. The adverse effects of mechanical ventilation are direct consequences of the changes in pulmonary airway pressures and intrathoracic volume changes induced by the repetitive mechanical cycles in a diseased lung. In this article, we review 14 major successful and unsuccessful randomized controlled trials conducted in patients with ARDS on a series of techniques to improve oxygenation and ventilation published since 2010. Those trials tested the effects of adjunctive therapies (neuromuscular blocking agents, prone positioning), methods for selecting the optimum positive end-expiratory pressure (after recruitment maneuvers, or guided by esophageal pressure), high-frequency oscillatory ventilation, extracorporeal oxygenation, and pharmacologic immune modulators of the pulmonary and systemic inflammatory responses in patients affected by ARDS. We will briefly comment physiology-based gaps of negative trials and highlight the possible needs to address in future clinical trials in ARDS.

Comparison between capnodynamic and thermodilution method for cardiac output monitoring during major abdominal surgery: An observational study.

BACKGROUND: Cardiac output (CO) monitoring is the basis of goal-directed treatment for major abdominal surgery. A capnodynamic method estimating cardiac output (COEPBF) by continuously calculating nonshunted pulmonary blood flow has previously shown good agreement and trending ability when evaluated in mechanically ventilated pigs. OBJECTIVES: To compare the performance of the capnodynamic method of CO monitoring with transpulmonary thermodilution (COTPTD) in patients undergoing major abdominal surgery. DESIGN: Prospective, observational, method comparison study. Simultaneous measurements of COEPBF and COTPTD were performed before incision at baseline and before and after increased (+10 cmH2O) positive end-expiratory pressure (PEEP), activation of epidural anaesthesia and intra-operative events of hypovolemia and low CO. The first 25 patients were ventilated with PEEP 5 cmH2O (PEEP5), while in the last 10 patients, lung recruitment followed by individual PEEP adjustment (PEEPadj) was performed before protocol start. SETTING: Karolinska University Hospital, Stockholm, Sweden. PATIENTS: In total, 35 patients (>18 years) scheduled for major abdominal surgery with advanced hemodynamic monitoring were included in the study. MAIN OUTCOME MEASURES AND ANALYSIS: Agreement and trending ability between COEPBF and COTPTD at different clinical moments were analysed with Bland--Altman and four quadrant plots. RESULTS: In total, 322 paired values, 227 in PEEP5 and 95 in PEEPadj were analysed. Respectively, the mean COEPBF and COTPTD were 4.5 ±â€Š1.0 and 4.8 ±â€Š1.1 in the PEEP5 group and 4.9 ±â€Š1.2 and 5.0 ±â€Š1.0 l min-1 in the PEEPadj group. Mean bias (levels of agreement) and percentage error (PE) were -0.2 (-2.2 to 1.7) l min-1 and 41% for the PEEP5 group and -0.1 (-1.7 to 1.5) l min-1 and 31% in the PEEPadj group. Concordance rates during changes in COEPBF and COTPTD were 92% in the PEEP5 group and 90% in the PEEPadj group. CONCLUSION: COEPBF provides continuous noninvasive CO estimation with acceptable performance, which improved after lung recruitment and PEEP adjustment, although not interchangeable with COTPTD. This method may become a tool for continuous intra-operative CO monitoring during general anaesthesia in the future. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03444545.

Monitoring Expired CO2 Kinetics to Individualize Lung-Protective Ventilation in Patients With the Acute Respiratory Distress Syndrome.

Mechanical ventilation (MV) is a lifesaving supportive intervention in the management of acute respiratory distress syndrome (ARDS), buying time while the primary precipitating cause is being corrected. However, MV can contribute to a worsening of the primary lung injury, known as ventilation-induced lung injury (VILI), which could have an important impact on outcome. The ARDS lung is characterized by diffuse and heterogeneous lung damage and is particularly prone to suffer the consequences of an excessive mechanical stress imposed by higher airway pressures and volumes during MV. Of major concern is cyclic overdistension, affecting those lung segments receiving a proportionally higher tidal volume in an overall reduced lung volume. Theoretically, healthier lung regions are submitted to a larger stress and cyclic deformation and thus at high risk for developing VILI. Clinicians have difficulties in detecting VILI, particularly cyclic overdistension at the bedside, since routine monitoring of gas exchange and lung mechanics are relatively insensitive to this mechanism of VILI. Expired CO2 kinetics integrates relevant pathophysiological information of high interest for monitoring. CO2 is produced by cell metabolism in large daily quantities. After diffusing to tissue capillaries, CO2 is transported first by the venous and then by pulmonary circulation to the lung. Thereafter diffusing from capillaries to lung alveoli, it is finally convectively transported by lung ventilation for its elimination to the atmosphere. Modern readily clinically available sensor technology integrates information related to pulmonary ventilation, perfusion, and gas exchange from the single analysis of expired CO2 kinetics measured at the airway opening. Current volumetric capnography (VCap), the representation of the volume of expired CO2 in one single breath, informs about pulmonary perfusion, end-expiratory lung volume, dead space, and pulmonary ventilation inhomogeneities, all intimately related to cyclic overdistension during MV. Additionally, the recently described capnodynamic method provides the possibility to continuously measure the end-expiratory lung volume and effective pulmonary blood flow. All this information is accessed non-invasively and breath-by-breath helping clinicians to personalize ventilatory settings at the bedside and minimize overdistension and cyclic deformation of lung tissue.

Prevention of atelectasis by continuous positive airway pressure in anaesthetised children: A randomised controlled study.

BACKGROUND: Continuous positive airway pressure (CPAP) prevents peri-operative atelectasis in adults, but its effect in children has not been quantified. OBJECTIVE: The aim of this study was to evaluate the role of CPAP in preventing postinduction and postoperative atelectasis in children under general anaesthesia. DESIGN: A randomised controlled study. SETTING: Single-institution study, community hospital, Mar del Plata. Argentina. PATIENTS: We studied 42 children, aged 6 months to 7 years, American Society of Anesthesiologists physical status class I, under standardised general anaesthesia. INTERVENTIONS: Patients were randomised into two groups: Control group (n = 21): induction and emergence of anaesthesia without CPAP; and CPAP group (n = 21): 5 cmH2O of CPAP during induction and emergence of anaesthesia. Lung ultrasound (LUS) imaging was performed before and 5 min after anaesthesia induction. Children without atelectasis were ventilated in the same manner as the Control group with standard ventilatory settings including 5 cmH2O of PEEP. Children with atelectasis received a recruitment manoeuvre followed by standard ventilation with 8 cmH2O of PEEP. Then, at the end of surgery, LUS images were repeated before tracheal extubation and 60 min after awakening. MAIN OUTCOME MEASURES: Lung aeration score and atelectasis assessed by LUS. RESULTS: Before anaesthesia, all children were free of atelectasis. After induction, 95% in the Control group developed atelectasis compared with 52% of patients in the CPAP group (P < 0.0001). LUS aeration scores were higher (impaired aeration) in the Control group than the CPAP group (8.8 ±â€Š3.8 vs. 3.5 ±â€Š3.3 points; P < 0.0001). At the end of surgery, before tracheal extubation, atelectasis was observed in 100% of children in the Control and 29% of the CPAP group (P < 0.0001) with a corresponding aeration score of 9.6 ±â€Š3.2 and 1.8 ±â€Š2.3, respectively (P < 0.0001). After surgery, 30% of children in the Control group and 10% in the CPAP group presented with residual atelectasis (P < 0.0001) also corresponding to a higher aeration score in the Control group (2.5 ±â€Š3.1) when compared with the CPAP group (0.5 ±â€Š1.5; P < 0.01). CONCLUSION: The use of 5 cmH2O of CPAP in healthy children of the studied age span during induction and emergence of anaesthesia effectively prevents atelectasis, with benefits maintained during the first postoperative hour. TRIAL REGISTRY: Clinicaltrials.gov NCT03461770.

Awake prone positioning does not reduce the risk of intubation in COVID-19 treated with high-flow nasal oxygen therapy: a multicenter, adjusted cohort study.

BACKGROUND: Awake prone positioning (awake-PP) in non-intubated coronavirus disease 2019 (COVID-19) patients could avoid endotracheal intubation, reduce the use of critical care resources, and improve survival. We aimed to examine whether the combination of high-flow nasal oxygen therapy (HFNO) with awake-PP prevents the need for intubation when compared to HFNO alone. METHODS: Prospective, multicenter, adjusted observational cohort study in consecutive COVID-19 patients with acute respiratory failure (ARF) receiving respiratory support with HFNO from 12 March to 9 June 2020. Patients were classified as HFNO with or without awake-PP. Logistic models were fitted to predict treatment at baseline using the following variables: age, sex, obesity, non-respiratory Sequential Organ Failure Assessment score, APACHE-II, C-reactive protein, days from symptoms onset to HFNO initiation, respiratory rate, and peripheral oxyhemoglobin saturation. We compared data on demographics, vital signs, laboratory markers, need for invasive mechanical ventilation, days to intubation, ICU length of stay, and ICU mortality between HFNO patients with and without awake-PP. RESULTS: A total of 1076 patients with COVID-19 ARF were admitted, of which 199 patients received HFNO and were analyzed. Fifty-five (27.6%) were pronated during HFNO; 60 (41%) and 22 (40%) patients from the HFNO and HFNO + awake-PP groups were intubated. The use of awake-PP as an adjunctive therapy to HFNO did not reduce the risk of intubation [RR 0.87 (95% CI 0.53-1.43), p = 0.60]. Patients treated with HFNO + awake-PP showed a trend for delay in intubation compared to HFNO alone [median 1 (interquartile range, IQR 1.0-2.5) vs 2 IQR 1.0-3.0] days (p = 0.055), but awake-PP did not affect 28-day mortality [RR 1.04 (95% CI 0.40-2.72), p = 0.92]. CONCLUSION: In patients with COVID-19 ARF treated with HFNO, the use of awake-PP did not reduce the need for intubation or affect mortality.

Efficacy of dexamethasone treatment for patients with the acute respiratory distress syndrome caused by COVID-19: study protocol for a randomized controlled superiority trial.

BACKGROUND: There are no specific generally accepted therapies for the coronavirus disease 2019 (COVID-19). The full spectrum of COVID-19 ranges from asymptomatic disease to mild respiratory tract illness to severe pneumonia, acute respiratory distress syndrome (ARDS), multisystem organ failure, and death. The efficacy of corticosteroids in viral ARDS remains unknown. We postulated that adjunctive treatment of established ARDS caused by COVID-19 with intravenous dexamethasone might change the pulmonary and systemic inflammatory response and thereby reduce morbidity, leading to a decrease in duration of mechanical ventilation and in mortality. METHODS/DESIGN: This is a multicenter, randomized, controlled, parallel, open-label, superiority trial testing dexamethasone in 200 mechanically ventilated adult patients with established moderate-to-severe ARDS caused by confirmed SARS-CoV-2 infection. Established ARDS is defined as maintaining a PaO2/FiO2 ≤ 200 mmHg on PEEP ≥ 10 cmH2O and FiO2 ≥ 0.5 after 12 ± 3 h of routine intensive care. Eligible patients will be randomly assigned to receive either dexamethasone plus standard intensive care or standard intensive care alone. Patients in the dexamethasone group will receive an intravenous dose of 20 mg once daily from day 1 to day 5, followed by 10 mg once daily from day 6 to day 10. The primary outcome is 60-day mortality. The secondary outcome is the number of ventilator-free days, defined as days alive and free from mechanical ventilation at day 28 after randomization. All analyses will be done according to the intention-to-treat principle. DISCUSSION: This study will assess the role of dexamethasone in patients with established moderate-to-severe ARDS caused by SARS-CoV-2. TRIAL REGISTRATION: ClinicalTrials.gov NCT04325061 . Registered on 25 March 2020 as DEXA-COVID19.

Clinical features, ventilatory management, and outcome of ARDS caused by COVID-19 are similar to other causes of ARDS.

PURPOSE: The main characteristics of mechanically ventilated ARDS patients affected with COVID-19, and the adherence to lung-protective ventilation strategies are not well known. We describe characteristics and outcomes of confirmed ARDS in COVID-19 patients managed with invasive mechanical ventilation (MV). METHODS: This is a multicenter, prospective, observational study in consecutive, mechanically ventilated patients with ARDS (as defined by the Berlin criteria) affected with with COVID-19 (confirmed SARS-CoV-2 infection in nasal or pharyngeal swab specimens), admitted to a network of 36 Spanish and Andorran intensive care units (ICUs) between March 12 and June 1, 2020. We examined the clinical features, ventilatory management, and clinical outcomes of COVID-19 ARDS patients, and compared some results with other relevant studies in non-COVID-19 ARDS patients. RESULTS: A total of 742 patients were analysed with complete 28-day outcome data: 128 (17.1%) with mild, 331 (44.6%) with moderate, and 283 (38.1%) with severe ARDS. At baseline, defined as the first day on invasive MV, median (IQR) values were: tidal volume 6.9 (6.3-7.8) ml/kg predicted body weight, positive end-expiratory pressure 12 (11-14) cmH2O. Values of respiratory system compliance 35 (27-45) ml/cmH2O, plateau pressure 25 (22-29) cmH2O, and driving pressure 12 (10-16) cmH2O were similar to values from non-COVID-19 ARDS patients observed in other studies. Recruitment maneuvers, prone position and neuromuscular blocking agents were used in 79%, 76% and 72% of patients, respectively. The risk of 28-day mortality was lower in mild ARDS [hazard ratio (RR) 0.56 (95% CI 0.33-0.93), p = 0.026] and moderate ARDS [hazard ratio (RR) 0.69 (95% CI 0.47-0.97), p = 0.035] when compared to severe ARDS. The 28-day mortality was similar to other observational studies in non-COVID-19 ARDS patients. CONCLUSIONS: In this large series, COVID-19 ARDS patients have features similar to other causes of ARDS, compliance with lung-protective ventilation was high, and the risk of 28-day mortality increased with the degree of ARDS severity.