The Use of the Oxygenation Stretch Index to Predict Outcomes in Mechanically Ventilated Patients With COVID-19 ARDS.

BACKGROUND: In ARDS caused by COVID-19 pneumonia, appropriate adjustment of physiologic parameters based on lung stretch or oxygenation may optimize the ventilatory strategy. This study aims to describe the prognostic performance on 60-d mortality of single and composite respiratory variables in subjects with COVID-19 ARDS who are on mechanical ventilation with a lung-protective strategy, including the oxygenation stretch index combining oxygenation and driving pressure (ΔP). METHODS: This single-center observational cohort study enrolled 166 subjects on mechanical ventilation and diagnosed with COVID-19 ARDS. We evaluated their clinical and physiologic characteristics. The primary study outcome was 60-d mortality. Prognostic factors were evaluated through receiver operating characteristic analysis, Cox proportional hazards regression model, and Kaplan-Meier survival curves. RESULTS: Mortality at day 60 was 18.1%, and hospital mortality was 22.9%. Oxygenation, ΔP, and composite variables were tested: oxygenation stretch index ([Formula: see text]/[Formula: see text] divided by ΔP) and ΔP × 4 + breathing frequency (f) (ΔP × 4 + f). At both day 1 and day 2 after inclusion, the oxygenation stretch index had the best area under the receiver operating characteristic curve (oxygenation stretch index on day 1 0.76 (95% CI 0.67-0.84) and on day 2 0.83 (95% CI 0.76-0.91) to predict 60-d mortality, although without significant difference from other indexes. In multivariable Cox regression, ΔP, [Formula: see text]/[Formula: see text], ΔP × 4 + f, and oxygenation stretch index were all associated with 60-d mortality. When dichotomizing the variables, ΔP ≥ 14, [Formula: see text]/[Formula: see text] ≤ 152 mm Hg, ΔP × 4 + f ≥ 80, and oxygenation stretch index < 7.7 showed lower 60-d survival probability. At day 2, after optimization of ventilatory settings, the subjects who persisted with the worse cutoff values for the oxygenation stretch index showed a lower probability of survival at 60 d compared with day 1; this was not the case for other parameters. CONCLUSIONS: The oxygenation stretch index, which combines [Formula: see text]/[Formula: see text] and ΔP, is associated with mortality and may be useful to predict clinical outcomes in COVID-19 ARDS.

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.

Mean Airway Pressure As a Predictor of 90-Day Mortality in Mechanically Ventilated Patients.

OBJECTIVES: To determine the association between mean airway pressure and 90-day mortality in patients with acute respiratory failure requiring mechanical ventilation and to compare the predictive ability of mean airway pressure compared with inspiratory plateau pressure and driving pressure. DESIGN: Prospective observational cohort. SETTING: Five ICUs in Lima, Peru. SUBJECTS: Adults requiring invasive mechanical ventilation via endotracheal tube for acute respiratory failure. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of potentially eligible participants (n = 1,500), 65 (4%) were missing baseline mean airway pressure, while 352 (23.5%) were missing baseline plateau pressure and driving pressure. Ultimately, 1,429 participants were included in the analysis with an average age of 59 ± 19 years, 45% female, and a mean PaO2/FIO2 ratio of 248 ± 147 mm Hg at baseline. Overall, 90-day mortality was 50.4%. Median baseline mean airway pressure was 13 cm H2O (interquartile range, 10-16 cm H2O) in participants who died compared to a median mean airway pressure of 12 cm H2O (interquartile range, 10-14 cm H2O) in participants who survived greater than 90 days (p < 0.001). Mean airway pressure was independently associated with 90-day mortality (odds ratio, 1.38 for difference comparing the 75th to the 25th percentile for mean airway pressure; 95% CI, 1.10-1.74) after adjusting for age, sex, baseline Acute Physiology and Chronic Health Evaluation III, baseline PaO2/FIO2 (modeled with restricted cubic spline), baseline positive end-expiratory pressure, baseline tidal volume, and hospital site. In predicting 90-day mortality, baseline mean airway pressure demonstrated similar discriminative ability (adjusted area under the curve = 0.69) and calibration characteristics as baseline plateau pressure and driving pressure. CONCLUSIONS: In a multicenter prospective cohort, baseline mean airway pressure was independently associated with 90-day mortality in mechanically ventilated participants and predicts mortality similarly to plateau pressure and driving pressure. Because mean airway pressure is readily available on all mechanically ventilated patients and all ventilator modes, it is a potentially more useful predictor of mortality in acute respiratory failure.

Premature, Opportune, and Delayed Weaning in Mechanically Ventilated Patients: A Call for Implementation of Weaning Protocols in Low- and Middle-Income Countries.

OBJECTIVES: Weaning protocols establish readiness-to-wean criteria to determine the opportune moment to conduct a spontaneous breathing trial. Weaning protocols have not been widely adopted or evaluated in ICUs in low- and middle-income countries. We sought to compare clinical outcomes between participants whose weaning trials were retrospectively determined to have been premature, opportune, or delayed based on when they met readiness-to-wean criteria. DESIGN: Prospective, multicenter observational study. SETTING: Five medical ICUs in four public hospitals in Lima, Perú. SUBJECTS: Adults with acute respiratory failure and at least 24 hours of invasive mechanical ventilation (n = 1,657). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We established six readiness-to-wean criteria and retrospectively categorized our sample into three weaning groups: 1) premature: if the weaning trial took place before fulfilling all criteria, 2) opportune: if the weaning trial took place within 24 hours after fulfilling the criteria, and 3) delayed: if the weaning trial took place over 24 hours after fulfilling criteria. We compared 90-day mortality, ventilator-free days, ICU-free days, and hospital-free days between premature, opportune, and delayed weaning groups. In our sample, 761 participants (60.8%) were classified as having a premature weaning trial, 196 underwent opportune weaning (15.7%), and 295 experienced delayed weaning (23.6%). There was no significant difference in 90-day mortality between the groups. Both the premature and delayed weaning groups had poorer clinical outcomes with fewer ventilator-free days (-2.18, p = 0.008) and (-3.49, p < 0.001), ICU-free days (-2.25, p = 0.001) and (-3.72, p < 0.001), and hospital-free days (-2.76, p = 0.044) and (-4.53, p = 0.004), respectively, compared with the opportune weaning group. CONCLUSIONS: Better clinical outcomes occur with opportune weaning compared with premature and delayed weaning. If readiness-to-wean criteria can be applied in resource-limited settings, it may improve ICU outcomes associated with opportune weaning.

Risk factors for the development of acute respiratory distress syndrome in mechanically ventilated adults in Peru: a multicenter observational study.

BACKGROUND: Clinical and epidemiological differences between acute respiratory distress syndrome (ARDS) that presents at the initiation of mechanical ventilation [MV] (ARDS at MV onset) and that which develops during the course of MV (ARDS after MV onset) are not well understood. We conducted an observational study in five Peruvian ICUs to characterize differences between ARDS at MV onset and after MV onset and identify risk factors for the development of ARDS after MV onset. METHODS: We consecutively enrolled critically ill patients with acute respiratory failure requiring at least 24 h of mechanical ventilation and followed them prospectively during the first 28 days and compared baseline characteristics and clinical outcomes by ARDS status. RESULTS: We enrolled 1657 participants on MV (mean age 60.0 years, 55% males) of whom 334 (20.2%) had ARDS at MV onset and 180 (10.9%) developed ARDS after MV onset. Average tidal volume at the initiation of MV was 8.7 mL/kg of predicted body weight (PBW) for participants with ARDS at MV onset, 8.6 mL/kg PBW for those who developed ARDS after MV onset, and 8.5 mL/kg PBW for those who never developed ARDS (p = 0.23). Overall, 90-day mortality was 56% and 55% for ARDS after MV onset and ARDS at MV onset, respectively, as compared to 46% among those who never developed ARDS (p < 0.01). Adults with ARDS had a higher body mass index (BMI) than those without ARDS (27.3 vs 26.5 kg/m2, p < 0.01). Higher peak pressure (adjusted interquartile OR = 1.51, 95% CI 1.21-1.88), higher mean airway pressure (adjusted interquartile OR = 1.41, 95% CI 1.13-1.76), and higher positive end-expiratory pressure (adjusted interquartile OR = 1.29, 95% CI 1.10-1.50) at MV onset were associated with a higher odds of developing ARDS after MV onset. CONCLUSIONS: In this study of mechanically ventilated patients, 31% of study participants had ARDS at some point during their ICU stay. Optimal lung-protective ventilation was not used in a majority of patients. Patients with ARDS after MV onset had a similar 90-day mortality as those with ARDS at MV onset. Higher airway pressures at MV onset, higher PEEP, and higher BMI were associated with the development of ARDS after MV onset.

Sedation practices and clinical outcomes in mechanically ventilated patients in a prospective multicenter cohort.

OBJECTIVES: We sought to study the association between sedation status, medications (benzodiazepines, opioids, and antipsychotics), and clinical outcomes in a resource-limited setting. DESIGN: A longitudinal study of critically ill participants on mechanical ventilation. SETTING: Five intensive care units (ICUs) in four public hospitals in Lima, Peru. PATIENTS: One thousand six hundred fifty-seven critically ill participants were assessed daily for sedation status during 28 days and vital status by day 90. RESULTS: After excluding data of participants without a Richmond Agitation Sedation Scale score and without sedation, we followed 1338 (81%) participants longitudinally for 18,645 ICU days. Deep sedation was present in 98% of participants at some point of the study and in 12,942 ICU days. Deep sedation was associated with higher mortality (interquartile odds ratio (OR) = 5.42, 4.23-6.95; p < 0.001) and a significant decrease in ventilator (- 7.27; p < 0.001), ICU (- 4.38; p < 0.001), and hospital (- 7.00; p < 0.001) free days. Agitation was also associated with higher mortality (OR = 39.9, 6.53-243, p < 0.001). The most commonly used sedatives were opioids and benzodiazepines (9259 and 8453 patient days respectively), and the latter were associated with a 41% higher mortality in participants with a higher cumulative dose (75th vs 25th percentile, interquartile OR = 1.41, 1.12-1.77; p < 0.01). The overall cumulative dose of benzodiazepines and opioids was high, 774.5 mg and 16.8 g, respectively, by day 7 and by day 28; these doses approximately doubled. Haloperidol was only used in 3% of ICU days; however, the use of it was associated with a 70% lower mortality (interquartile OR = 0.3, 0.22-0.44, p < 0.001). CONCLUSIONS: Deep sedation, agitation, and cumulative dose of benzodiazepines were all independently associated with higher 90-day mortality. Additionally, deep sedation was associated with less ventilator-, ICU-, and hospital-free days. In contrast, haloperidol was associated with lower mortality in our study.

Quantitative Dual-Energy Computed Tomography Predicts Regional Perfusion Heterogeneity in a Model of Acute Lung Injury.

OBJECTIVE: The aims of this study were to investigate the ability of contrast-enhanced dual-energy computed tomography (DECT) for assessing regional perfusion in a model of acute lung injury, using dynamic first-pass perfusion CT (DynCT) as the criterion standard and to evaluate if changes in lung perfusion caused by prone ventilation are similarly demonstrated by DECT and DynCT. METHODS: This was an institutional review board-approved study, compliant with guidelines for humane care of laboratory animals. A ventilator-induced lung injury protocol was applied to 6 landrace pigs. Perfused blood volume (PBV) and pulmonary blood flow (PBF) were respectively quantified by DECT and DynCT, in supine and prone positions. The lungs were segmented in equally sized regions of interest, namely, dorsal, middle, and ventral. Perfused blood volume and PBF values were normalized by lung density. Regional air fraction (AF) was assessed by triple-material decomposition DECT. Per-animal correlation between PBV and PBF was assessed with Pearson R. Regional differences in PBV, PBF, and AF were evaluated with 1-way analysis of variance and post hoc linear trend analysis (α = 5%). RESULTS: Mean correlation coefficient between PBV and PBF was 0.70 (range, 0.55-0.98). Higher PBV and PBF values were observed in dorsal versus ventral regions. Dorsal-to-ventral linear trend slopes were -10.24 mL/100 g per zone for PBV (P < 0.001) and -223.0 mL/100 g per minute per zone for PBF (P < 0.001). Prone ventilation also revealed higher PBV and PBF in dorsal versus ventral regions. Dorsal-to-ventral linear trend slopes were -16.16 mL/100 g per zone for PBV (P < 0.001) and -108.2 mL/100 g per minute per zone for PBF (P < 0.001). By contrast, AF was lower in dorsal versus ventral regions in supine position, with dorsal-to-ventral linear trend slope of +5.77%/zone (P < 0.05). Prone ventilation was associated with homogenization of AF distribution among different regions (P = 0.74). CONCLUSIONS: Dual-energy computed tomography PBV is correlated with DynCT-PBF in a model of acute lung injury, and able to demonstrate regional differences in pulmonary perfusion. Perfusion was higher in the dorsal regions, irrespectively to decubitus, with more homogeneous lung aeration in prone position.

Esophageal Manometry and Regional Transpulmonary Pressure in Lung Injury.

RATIONALE: Esophageal manometry is the clinically available method to estimate pleural pressure, thus enabling calculation of transpulmonary pressure (Pl). However, many concerns make it uncertain in which lung region esophageal manometry reflects local Pl. OBJECTIVES: To determine the accuracy of esophageal pressure (Pes) and in which regions esophageal manometry reflects pleural pressure (Ppl) and Pl; to assess whether lung stress in nondependent regions can be estimated at end-inspiration from Pl. METHODS: In lung-injured pigs (n = 6) and human cadavers (n = 3), Pes was measured across a range of positive end-expiratory pressure, together with directly measured Ppl in nondependent and dependent pleural regions. All measurements were obtained with minimal nonstressed volumes in the pleural sensors and esophageal balloons. Expiratory and inspiratory Pl was calculated by subtracting local Ppl or Pes from airway pressure; inspiratory Pl was also estimated by subtracting Ppl (calculated from chest wall and respiratory system elastance) from the airway plateau pressure. MEASUREMENTS AND MAIN RESULTS: In pigs and human cadavers, expiratory and inspiratory Pl using Pes closely reflected values in dependent to middle lung (adjacent to the esophagus). Inspiratory Pl estimated from elastance ratio reflected the directly measured nondependent values. CONCLUSIONS: These data support the use of esophageal manometry in acute respiratory distress syndrome. Assuming correct calibration, expiratory Pl derived from Pes reflects Pl in dependent to middle lung, where atelectasis usually predominates; inspiratory Pl estimated from elastance ratio may indicate the highest level of lung stress in nondependent "baby" lung, where it is vulnerable to ventilator-induced lung injury.

Volume-controlled Ventilation Does Not Prevent Injurious Inflation during Spontaneous Effort.

RATIONALE: Spontaneous breathing during mechanical ventilation increases transpulmonary pressure and Vt, and worsens lung injury. Intuitively, controlling Vt and transpulmonary pressure might limit injury caused by added spontaneous effort. OBJECTIVES: To test the hypothesis that, during spontaneous effort in injured lungs, limitation of Vt and transpulmonary pressure by volume-controlled ventilation results in less injurious patterns of inflation. METHODS: Dynamic computed tomography was used to determine patterns of regional inflation in rabbits with injured lungs during volume-controlled or pressure-controlled ventilation. Transpulmonary pressure was estimated by using esophageal balloon manometry [Pl(es)] with and without spontaneous effort. Local dependent lung stress was estimated as the swing (inspiratory change) in transpulmonary pressure measured by intrapleural manometry in dependent lung and was compared with the swing in Pl(es). Electrical impedance tomography was performed to evaluate the inflation pattern in a larger animal (pig) and in a patient with acute respiratory distress syndrome. MEASUREMENTS AND MAIN RESULTS: Spontaneous breathing in injured lungs increased Pl(es) during pressure-controlled (but not volume-controlled) ventilation, but the pattern of dependent lung inflation was the same in both modes. In volume-controlled ventilation, spontaneous effort caused greater inflation and tidal recruitment of dorsal regions (greater than twofold) compared with during muscle paralysis, despite the same Vt and Pl(es). This was caused by higher local dependent lung stress (measured by intrapleural manometry). In injured lungs, esophageal manometry underestimated local dependent pleural pressure changes during spontaneous effort. CONCLUSIONS: Limitation of Vt and Pl(es) by volume-controlled ventilation could not eliminate harm caused by spontaneous breathing unless the level of spontaneous effort was lowered and local dependent lung stress was reduced.

Spontaneous Effort During Mechanical Ventilation: Maximal Injury With Less Positive End-Expiratory Pressure.

OBJECTIVES: We recently described how spontaneous effort during mechanical ventilation can cause "pendelluft," that is, displacement of gas from nondependent (more recruited) lung to dependent (less recruited) lung during early inspiration. Such transfer depends on the coexistence of more recruited (source) liquid-like lung regions together with less recruited (target) solid-like lung regions. Pendelluft may improve gas exchange, but because of tidal recruitment, it may also contribute to injury. We hypothesize that higher positive end-expiratory pressure levels decrease the propensity to pendelluft and that with lower positive end-expiratory pressure levels, pendelluft is associated with improved gas exchange but increased tidal recruitment. DESIGN: Crossover design. SETTING: University animal research laboratory. SUBJECTS: Anesthetized landrace pigs. INTERVENTIONS: Surfactant depletion was achieved by saline lavage in anesthetized pigs, and ventilator-induced lung injury was produced by ventilation with high tidal volume and low positive end-expiratory pressure. Ventilation was continued in each of four conditions: positive end-expiratory pressure (low or optimized positive end-expiratory pressure after recruitment) and spontaneous breathing (present or absent). Tidal recruitment was assessed using dynamic CT and regional ventilation/perfusion using electric impedance tomography. Esophageal pressure was measured using an esophageal balloon manometer. MEASUREMENTS AND RESULTS: Among the four conditions, spontaneous breathing at low positive end-expiratory pressure not only caused the largest degree of pendelluft, which was associated with improved ventilation/perfusion matching and oxygenation, but also generated the greatest tidal recruitment. At low positive end-expiratory pressure, paralysis worsened oxygenation but reduced tidal recruitment. Optimized positive end-expiratory pressure decreased the magnitude of spontaneous efforts (measured by esophageal pressure) despite using less sedation, from -5.6 ± 1.3 to -2.0 ± 0.7 cm H2O, while concomitantly reducing pendelluft and tidal recruitment. No pendelluft was observed in the absence of spontaneous effort. CONCLUSIONS: Spontaneous effort at low positive end-expiratory pressure improved oxygenation but promoted tidal recruitment associated with pendelluft. Optimized positive end-expiratory pressure (set after lung recruitment) may reverse the harmful effects of spontaneous breathing by reducing inspiratory effort, pendelluft, and tidal recruitment.

Establishment of a prospective cohort of mechanically ventilated patients in five intensive care units in Lima, Peru: protocol and organisational characteristics of participating centres.

INTRODUCTION: Mechanical ventilation is a cornerstone in the management of critically ill patients worldwide; however, less is known about the clinical management of mechanically ventilated patients in low and middle income countries where limitation of resources including equipment, staff and access to medical information may play an important role in defining patient-centred outcomes. We present the design of a prospective, longitudinal study of mechanically ventilated patients in Peru that aims to describe a large cohort of mechanically ventilated patients and identify practices that, if modified, could result in improved patient-centred outcomes and lower costs. METHODS AND ANALYSIS: Five Peruvian intensive care units (ICUs) and the Medical ICU at the Johns Hopkins Hospital were selected for this study. Eligible patients were those who underwent at least 24 h of invasive mechanical ventilation within the first 48 h of admission into the ICU. Information on ventilator settings, clinical management and treatment were collected daily for up to 28 days or until the patient was discharged from the unit. Vital status was assessed at 90 days post enrolment. A subset of participants who survived until hospital discharge were asked to participate in an ancillary study to assess vital status, and physical and mental health at 6, 12, 24 and 60 months after hospitalisation, Primary outcomes include 90-day mortality, time on mechanical ventilation, hospital and ICU lengths of stay, and prevalence of acute respiratory distress syndrome. In subsequent analyses, we aim to identify interventions and standardised care strategies that can be tailored to resource-limited settings and that result in improved patient-centred outcomes and lower costs. ETHICS AND DISSEMINATION: We obtained ethics approval from each of the four participating hospitals in Lima, Peru, and at the Johns Hopkins School of Medicine, Baltimore, USA. Results will be disseminated as several separate publications in different international journals.