Lung Protective Mechanical Ventilation in Severe Acute Brain Injured Patients: A Multicenter, Randomized Clinical Trial (PROLABI).

BACKGROUND: Lung protective strategies using low tidal volumes and moderate positive end expiratory pressures (PEEP) are considered best practice in critical care, but interventional trials have never been conducted in acutely brain-injured patients due to concerns about carbon dioxide control and effect of PEEP on cerebral hemodynamic. METHODS: In this multicenter, open-label, controlled clinical trial 190 adult acute brain injured patients were assigned to receive either a lung-protective or a conventional ventilatory strategy. The primary outcome was a composite endpoint of death, ventilator dependency and ARDS at day 28. Neurological outcome was assessed at intensive care unit discharge by Oxford Handicap Scale and at six months by Glasgow Outcome Scale. FINDINGS: The two study arms had similar characteristics at baseline. In the lung-protective and conventional strategy groups, using an intention-to-treat approach, the composite outcome at 28 days was 61.5% and 45.3% (RR 1.35; 95%CI 1.03-1.79; p=0.025). Mortality was 28.9% and 15.1% (RR 1.91; 95%CI 1.06-3.42; p=0.02), ventilator dependency was 42.3% and 27.9% (RR 1.52; 95%CI 1.01-2.28; p=0.039), and incidence of ARDS was 30.8% and 22.1% (RR 1.39; 95%CI 0.85-2.27; p=0.179) respectively. The trial was stopped after enrolling 190 subjects because of termination of funding. INTERPRETATION: In acutely brain-injured patients without ARDS a lung-protective ventilatory strategy as compared to a conventional strategy did not reduce mortality, percentage of patients weaned from mechanical ventilation, incidence of ARDS and was not beneficial in terms of neurological outcomes. Due to the early termination, these preliminary results require confirmation in larger trials. Clinical trial registration available at www. CLINICALTRIALS: gov, ID: NCT01690819.

Regional distribution of mechanical strain and macrophage-associated lung inflammation after ventilator-induced lung injury: an experimental study.

BACKGROUND: Alveolar macrophages activation to the pro-inflammatory phenotype M1 is pivotal in the pathophysiology of Ventilator-Induced Lung Injury (VILI). Increased lung strain is a known determinant of VILI, but a direct correspondence between regional lung strain and macrophagic activation remains unestablished. [68Ga]Ga-DOTA-TATE is a Positron Emission Tomography (PET) radiopharmaceutical with a high affinity for somatostatin receptor subtype 2 (SSTR2), which is overexpressed by pro-inflammatory-activated macrophages. Aim of the study was to determine, in a porcine model of VILI, whether mechanical strain correlates topographically with distribution of activated macrophages detected by [68Ga]Ga-DOTA-TATE uptake. METHODS: Seven anesthetized pigs underwent VILI, while three served as control. Lung CT scans were acquired at incremental tidal volumes, simultaneously recording lung mechanics. [68Ga]Ga-DOTA-TATE was administered, followed by dynamic PET scans. Custom MatLab scripts generated voxel-by-voxel gas volume and strain maps from CT slices at para-diaphragmatic (Para-D) and mid-thoracic (Mid-T) levels. Analysis of regional Voxel-associated Normal Strain (VoStrain) and [68Ga]Ga-DOTA-TATE uptake was performed and a measure of the statistical correlation between these two variables was quantified using the linear mutual information (LMI) method. RESULTS: Compared to controls, the VILI group exhibited statistically significant higher VoStrain and Standardized Uptake Value Ratios (SUVR) both at Para-D and Mid-T levels. Both VoStrain and SUVR increased along the gravitational axis with an increment described by statistically different regression lines between VILI and healthy controls and reaching the peak in the dependent regions of the lung (for strain in VILI vs. control was at Para-D: 760 ± 210 vs. 449 ± 106; at Mid-T level 497 ± 373 vs. 193 ± 160; for SUVR, in VILI vs. control was at Para-D: 2.2 ± 1.3 vs. 1.3 ± 0.1; at Mid-T level 1.3 ± 1.0 vs. 0.6 ± 0.03). LMI in both Para-D and Mid-T was statistically significantly higher in VILI than in controls. CONCLUSIONS: In this porcine model of VILI, we found a topographical correlation between lung strain and [68Ga]Ga-DOTA-TATE uptake at voxel level, suggesting that mechanical alteration and specific activation of inflammatory cells are strongly linked in VILI. This study represents the first voxel-by-voxel examination of this relationship in a multi-modal imaging analysis.

High PEEP with recruitment maneuvers versus Low PEEP During General Anesthesia for Surgery - a Bayesian individual patient data meta-analysis of three randomized clinical trials.

BACKGROUND: The influence of high positive end-expiratory pressure (PEEP) with recruitment maneuvers on the occurrence of postoperative pulmonary complications after surgery is still not definitively established. Bayesian analysis can help to gain further insights from the available data and provide a probabilistic framework that is easier to interpret. Our objective was to estimate the posterior probability that the use of high PEEP with recruitment maneuvers is associated with reduced postoperative pulmonary complications in patients with intermediate-to-high risk under neutral, pessimistic, and optimistic expectations regarding the treatment effect. METHODS: Multilevel Bayesian logistic regression analysis on individual patient data from three randomized clinical trials carried out on surgical patients at Intermediate-to-High Risk for postoperative pulmonary complications. The main outcome was the occurrence of postoperative pulmonary complications in the early postoperative period. We studied the effect of high PEEP with recruitment maneuvers versus Low PEEP Ventilation. Priors were chosen to reflect neutral, pessimistic, and optimistic expectations of the treatment effect. RESULTS: Using a neutral, pessimistic, or optimistic prior, the posterior mean odds ratio (OR) for High PEEP with recruitment maneuvers compared to Low PEEP was 0.85 (95% Credible Interval [CrI] 0.71 to 1.02), 0.87 (0.72 to 1.04), and 0.86 (0.71 to 1.02), respectively. Regardless of prior beliefs, the posterior probability of experiencing a beneficial effect exceeded 90%. Subgroup analysis indicated a more pronounced effect in patients who underwent laparoscopy (OR: 0.67 [0.50 to 0.87]) and those at high risk for PPCs (OR: 0.80 [0.53 to 1.13]). Sensitivity analysis, considering severe postoperative pulmonary complications only or applying a different heterogeneity prior, yielded consistent results. CONCLUSION: High PEEP with recruitment maneuvers demonstrated a moderate reduction in the probability of PPC occurrence, with a high posterior probability of benefit observed consistently across various prior beliefs, particularly among patients who underwent laparoscopy.

Stroke in critically ill patients with respiratory failure due to COVID-19: Disparities between low-middle and high-income countries.

PURPOSE: We aimed to compare the incidence of stroke in low-and middle-income countries (LMICs) versus high-income countries (HICs) in critically ill patients with COVID-19 and its impact on in-hospital mortality. METHODS: International observational study conducted in 43 countries. Stroke and mortality incidence rates and rate ratios (IRR) were calculated per admitted days using Poisson regression. Inverse probability weighting (IPW) was used to address the HICs vs. LMICs imbalance for confounders. RESULTS: 23,738 patients [20,511(86.4 %) HICs vs. 3,227(13.6 %) LMICs] were included. The incidence stroke/1000 admitted-days was 35.7 (95 %CI = 28.4-44.9) LMICs and 17.6 (95 %CI = 15.8-19.7) HICs; ischemic 9.47 (95 %CI = 6.57-13.7) LMICs, 1.97 (95 %CI = 1.53, 2.55) HICs; hemorrhagic, 7.18 (95 %CI = 4.73-10.9) LMICs, and 2.52 (95 %CI = 2.00-3.16) HICs; unspecified stroke type 11.6 (95 %CI = 7.75-17.3) LMICs, 8.99 (95 %CI = 7.70-10.5) HICs. In regression with IPW, LMICs vs. HICs had IRR = 1.78 (95 %CI = 1.31-2.42, p < 0.001). Patients from LMICs were more likely to die than those from HICs [43.6% vs 29.2 %; Relative Risk (RR) = 2.59 (95 %CI = 2.29-2.93), p < 0.001)]. Patients with stroke were more likely to die than those without stroke [RR = 1.43 (95 %CI = 1.19-1.72), p < 0.001)]. CONCLUSIONS: Stroke incidence was low in HICs and LMICs although the stroke risk was higher in LMICs. Both LMIC status and stroke increased the risk of death. Improving early diagnosis of stroke and redistribution of healthcare resources should be a priority. TRIAL REGISTRATION: ACTRN12620000421932 registered on 30/03/2020.

Towards the automatic calculation of the EQUAL Candida Score: Extraction of CVC-related information from EMRs of critically ill patients with candidemia in Intensive Care Units.

OBJECTIVES: Candidemia is the most frequent invasive fungal disease and the fourth most frequent bloodstream infection in hospitalized patients. Its optimal management is crucial for improving patients' survival. The quality of candidemia management can be assessed with the EQUAL Candida Score. The objective of this work is to support its automatic calculation by extracting central venous catheter-related information from Italian text in clinical notes of electronic medical records. MATERIALS AND METHODS: The sample includes 4,787 clinical notes of 108 patients hospitalized between January 2018 to December 2020 in the Intensive Care Units of the IRCCS San Martino Polyclinic Hospital in Genoa (Italy). The devised pipeline exploits natural language processing (NLP) to produce numerical representations of clinical notes used as input of machine learning (ML) algorithms to identify CVC presence and removal. It compares the performances of (i) rule-based method, (ii) count-based method together with a ML algorithm, and (iii) a transformers-based model. RESULTS: Results, obtained with three different approaches, were evaluated in terms of weighted F1 Score. The random forest classifier showed the higher performance in both tasks reaching 82.35%. CONCLUSION: The present work constitutes a first step towards the automatic calculation of the EQUAL Candida Score from unstructured daily collected data by combining ML and NLP methods. The automatic calculation of the EQUAL Candida Score could provide crucial real-time feedback on the quality of candidemia management, aimed at further improving patients' health.

Transpulmonary pressure monitoring in critically ill patients: pros and cons.

The use of transpulmonary pressure monitoring based on measurement of esophageal pressure has contributed importantly to the personalization of mechanical ventilation based on respiratory pathophysiology in critically ill patients. However, esophageal pressure monitoring is still underused in the clinical practice. This technique allows partitioning of the respiratory mechanics between the lungs and the chest wall, provides information on lung recruitment and risk of barotrauma, and helps titrating mechanical ventilation settings in patients with respiratory failure. In assisted ventilation modes and during non-invasive respiratory support, esophageal pressure monitoring provides important information on the inspiratory effort and work of breathing. Nonetheless, several controversies persist on technical aspects, interpretation and clinical decision-making based on values derived from this monitoring technique. The aim of this review is to summarize the physiological bases of esophageal pressure monitoring, discussing the pros and cons of its clinical applications and different interpretations in critically ill patients undergoing invasive and non-invasive respiratory support.

Comparison between high-flow nasal oxygen (HFNO) alternated with non-invasive ventilation (NIV) and HFNO and NIV alone in patients with COVID-19: a retrospective cohort study.

BACKGROUND: Non-invasive respiratory support (conventional oxygen therapy [COT], non-invasive ventilation [NIV], high-flow nasal oxygen [HFNO], and NIV alternated with HFNO [NIV + HFNO] may reduce the need for invasive mechanical ventilation (IMV) in patients with COVID-19. The outcome of patients treated non-invasively depends on clinical severity at admission. We assessed the need for IMV according to NIV, HFNO, and NIV + HFNO in patients with COVID-19 according to disease severity and evaluated in-hospital survival rates and hospital and intensive care unit (ICU) lengths of stay. METHODS: This cohort study was conducted using data collected between March 2020 and July 2021. Patients ≥ 18 years admitted to the ICU with a diagnosis of COVID-19 were included. Patients hospitalized for < 3 days, receiving therapy (COT, NIV, HFNO, or NIV + HFNO) for < 48 h, pregnant, and with no primary outcome data were excluded. The COT group was used as reference for multivariate Cox regression model adjustment. RESULTS: Of 1371 patients screened, 958 were eligible: 692 (72.2%) on COT, 92 (9.6%) on NIV, 31 (3.2%) on HFNO, and 143 (14.9%) on NIV + HFNO. The results for the patients in each group were as follows: median age (interquartile range): NIV (64 [49-79] years), HFNO (62 [55-70] years), NIV + HFNO (62 [48-72] years) (p = 0.615); heart failure: NIV (54.5%), HFNO (36.3%), NIV + HFNO (9%) (p = 0.003); diabetes mellitus: HFNO (17.6%), NIV + HFNO (44.7%) (p = 0.048). > 50% lung damage on chest computed tomography (CT): NIV (13.3%), HFNO (15%), NIV + HFNO (71.6%) (p = 0.038); SpO2/FiO2: NIV (271 [118-365] mmHg), HFNO (317 [254-420] mmHg), NIV + HFNO (229 [102-317] mmHg) (p = 0.001); rate of IMV: NIV (26.1%, p = 0.002), HFNO (22.6%, p = 0.023), NIV + HFNO (46.8%); survival rate: HFNO (83.9%), NIV + HFNO (63.6%) (p = 0.027); ICU length of stay: NIV (8.5 [5-14] days), NIV + HFNO (15 [10-25] days (p < 0.001); hospital length of stay: NIV (13 [10-21] days), NIV + HFNO (20 [15-30] days) (p < 0.001). After adjusting for comorbidities, chest CT score and SpO2/FiO2, the risk of IMV in patients on NIV + HFNO remained high (hazard ratio, 1.88; 95% confidence interval, 1.17-3.04). CONCLUSIONS: In patients with COVID-19, NIV alternating with HFNO was associated with a higher rate of IMV independent of the presence of comorbidities, chest CT score and SpO2/FiO2. Trial registration ClinicalTrials.gov identifier: NCT05579080.

Dyspnoea in acutely ill mechanically ventilated adult patients: an ERS/ESICM statement.

This statement outlines a review of the literature and current practice concerning the prevalence, clinical significance, diagnosis and management of dyspnoea in critically ill, mechanically ventilated adult patients. It covers the definition, pathophysiology, epidemiology, short- and middle-term impact, detection and quantification, and prevention and treatment of dyspnoea. It represents a collaboration of the European Respiratory Society (ERS) and the European Society of Intensive Care Medicine (ESICM). Dyspnoea ranks among the most distressing experiences that human beings can endure. Approximately 40% of patients undergoing invasive mechanical ventilation in the intensive care unit (ICU) report dyspnoea, with an average intensity of 45 mm on a visual analogue scale from 0 to 100 mm. Although it shares many similarities with pain, dyspnoea can be far worse than pain in that it summons a primal fear response. As such, it merits universal and specific consideration. Dyspnoea must be identified, prevented and relieved in every patient. In the ICU, mechanically ventilated patients are at high risk of experiencing breathing difficulties because of their physiological status and, in some instances, because of mechanical ventilation itself. At the same time, mechanically ventilated patients have barriers to signalling their distress. Addressing this major clinical challenge mandates teaching and training, and involves ICU caregivers and patients. This is even more important because, as opposed to pain which has become a universal healthcare concern, very little attention has been paid to the identification and management of respiratory suffering in mechanically ventilated ICU patients.

Dyspnoea in acutely ill mechanically ventilated adult patients: an ERS/ESICM statement.

This statement outlines a review of the literature and current practice concerning the prevalence, clinical significance, diagnosis and management of dyspnoea in critically ill, mechanically ventilated adult patients. It covers the definition, pathophysiology, epidemiology, short- and middle-term impact, detection and quantification, and prevention and treatment of dyspnoea. It represents a collaboration of the European Respiratory Society and the European Society of Intensive Care Medicine. Dyspnoea ranks among the most distressing experiences that human beings can endure. Approximately 40% of patients undergoing invasive mechanical ventilation in the intensive care unit (ICU) report dyspnoea, with an average intensity of 45 mm on a visual analogue scale from 0 to 100 mm. Although it shares many similarities with pain, dyspnoea can be far worse than pain in that it summons a primal fear response. As such, it merits universal and specific consideration. Dyspnoea must be identified, prevented and relieved in every patient. In the ICU, mechanically ventilated patients are at high risk of experiencing breathing difficulties because of their physiological status and, in some instances, because of mechanical ventilation itself. At the same time, mechanically ventilated patients have barriers to signalling their distress. Addressing this major clinical challenge mandates teaching and training, and involves ICU caregivers and patients. This is even more important because, as opposed to pain which has become a universal healthcare concern, very little attention has been paid to the identification and management of respiratory suffering in mechanically ventilated ICU patients.

Follow-up short and long-term mortalities of tracheostomized critically ill patients in an Italian multi-center observational study.

The effects of tracheostomy on outcome as well as on intra or post-operative complications is yet to be defined. Admission of patients with tracheostomy to rehabilitation facility is at higher risk of suboptimal care and increased mortality. The aim of the study was to investigate ICU mortality, clinical outcome and quality of life up to 12 months after ICU discharge in tracheostomized critically ill patients. This is a prospective, multi-center, cohort study endorsed by Italian Society of Anesthesia, Analgesia, Reanimation, and Intensive Care (SIAARTI Prot. n° 643/13) registered in Clinicaltrial.gov (NCT01899352). Patients admitted to intensive care unit (ICU) and requiring elective tracheostomy according to physician in charge decision were included in the study. The primary outcome was ICU mortality. Secondary outcomes included risk factors for ICU mortality, prevalence of mortality at follow-up, rate of discharge from the hospital and rehabilitation, quality of life, performance status, and management of tracheostomy cannula at 3-, 6, 12-months from the day of tracheostomy. 694 critically ill patients who were tracheostomized in the ICU were included. ICU mortality was 15.8%. Age, SOFA score at the day of the tracheostomy, and days of endotracheal intubation before tracheostomy were risk factors for ICU mortality. The regression tree analysis showed that SOFA score at the day of tracheostomy and age had a preeminent role for the choice to perform the tracheostomy. Of the 694 ICU patients with tracheostomy, 469 completed the 12-months follow-up. Mortality was 33.51% at 3-months, 45.30% at 6-months, and 55.86% at 12-months. Patients with tracheostomy were less likely discharged at home but at hospital facilities or rehabilitative structures; and quality of life of patients with tracheostomy was severely compromised at 3-6 and 12 months when compared with patients without tracheostomy. In patients admitted to ICU, tracheostomy is associated with high mortality, difficult rehabilitation, and decreased quality of life. The choice to perform a tracheostomy should be carefully weighed on family burden and health-related quality of life.Clinical trial registration: Clinicaltrial.gov (NCT01899352).

Individualized Thresholds of Hypoxemia and Hyperoxemia and their Effect on Outcome in Acute Brain Injured Patients: A Secondary Analysis of the ENIO Study.

BACKGROUND: In acute brain injury (ABI), the effects of hypoxemia as a potential cause of secondary brain damage and poor outcome are well documented, whereas the impact of hyperoxemia is unclear. The primary aim of this study was to assess the episodes of hypoxemia and hyperoxemia in patients with ABI during the intensive care unit (ICU) stay and to determine their association with in-hospital mortality. The secondary aim was to identify the optimal thresholds of arterial partial pressure of oxygen (PaO2) predicting in-hospital mortality. METHODS: We conducted a secondary analysis of a prospective multicenter observational cohort study. Adult patients with ABI (traumatic brain injury, subarachnoid aneurysmal hemorrhage, intracranial hemorrhage, ischemic stroke) with available data on PaO2 during the ICU stay were included. Hypoxemia was defined as PaO2 < 80 mm Hg, normoxemia was defined as PaO2 between 80 and 120 mm Hg, mild/moderate hyperoxemia was defined as PaO2 between 121 and 299 mm Hg, and severe hyperoxemia was defined as PaO2 levels ≥ 300 mm Hg. RESULTS: A total of 1,407 patients were included in this study. The mean age was 52 (±18) years, and 929 (66%) were male. Over the ICU stay, the fractions of patients in the study cohort who had at least one episode of hypoxemia, mild/moderate hyperoxemia, and severe hyperoxemia were 31.3%, 53.0%, and 1.7%, respectively. PaO2 values below 92 mm Hg and above 156 mm Hg were associated with an increased probability of in-hospital mortality. Differences were observed among subgroups of patients with ABI, with consistent effects only seen in patients without traumatic brain injury. CONCLUSIONS: In patients with ABI, hypoxemia and mild/moderate hyperoxemia were relatively frequent. Hypoxemia and hyperoxemia during ICU stay may influence in-hospital mortality. However, the small number of oxygen values collected represents a major limitation of the study.

Incidence and Outcomes of Acute Respiratory Distress Syndrome in Brain-Injured Patients Receiving Invasive Ventilation: A Secondary Analysis of the ENIO Study.

Background: Acute respiratory distress syndrome (ARDS) is an important pulmonary complication in brain-injured patients receiving invasive mechanical ventilation (IMV). We aimed to evaluate the incidence and association between ARDS and clinical outcomes in patients with different forms of acute brain injury requiring IMV in the intensive care unit (ICU). Methods: This was a preplanned secondary analysis of a prospective, multicenter, international cohort study (NCT03400904). We included brain-injured patients receiving IMV for ≥ 24 h. ARDS was the main exposure of interest and was identified during index ICU admission using the Berlin definition. We examined the incidence and adjusted association of ARDS with ICU mortality, ICU length of stay, duration of IMV, and extubation failure. Outcomes were evaluated using mixed-effect logistic regression and cause-specific Cox proportional hazards models. Results: 1492 patients from 67 hospitals and 16 countries were included in the analysis, of whom 137 individuals developed ARDS (9.2% of overall cohort). Across countries, the median ARDS incidence was 5.1% (interquartile range [IQR] 0-10; range 0-27.3). ARDS was associated with increased ICU mortality (adjusted odds ratio (OR) 2.66; 95% confidence interval [CI], 1.29-5.48), longer ICU length of stay (adjusted hazard ratio [HR] 0.59; 95% CI, 0.48-0.73), and longer duration of IMV (adjusted HR 0.54; 95% CI, 0.44-0.67). The association between ARDS and extubation failure approached statistical significance (adjusted HR 1.48; 95% CI 0.99-2.21). Higher ARDS severity was associated with incrementally longer ICU length of stay and longer cumulative duration of IMV. Findings remained robust in a sensitivity analysis evaluating the magnitude of unmeasured confounding. Conclusions: In this cohort of acutely brain-injured patients, the incidence of ARDS was similar to that reported in other mixed cohorts of critically ill patients. Development of ARDS was associated with worse outcomes.

Effects of positive end-expiratory pressure on brain oxygenation, systemic oxygen cascade and metabolism in acute brain injured patients: a pilot physiological cross-sectional study.

Patients with acute brain injury (ABI) often require the application of positive end-expiratory pressure (PEEP) to optimize mechanical ventilation and systemic oxygenation. However, the effect of PEEP on cerebral function and metabolism is unclear. The primary aim of this study was to evaluate the effects of PEEP augmentation test (from 5 to 15 cmH2O) on brain oxygenation, systemic oxygen cascade and metabolism in ABI patients. Secondary aims include to determine whether changes in regional cerebral oxygenation are reflected by changes in oxygenation cascade and metabolism, and to assess the correlation between brain oxygenation and mechanical ventilation settings. Single center, pilot cross-sectional observational study in an Academic Hospital. Inclusion criteria were: adult (> 18 y/o) patients with ABI and stable intracranial pressure, available gas exchange and indirect calorimetry (IC) monitoring. Cerebral oxygenation was monitored with near-infrared spectroscopy (NIRS) and different derived parameters were collected: variation (Δ) in oxy (O2)-hemoglobin (Hb) (ΔO2Hbi), deoxy-Hb(ΔHHbi), total-Hb(ΔcHbi), and total regional oxygenation (ΔrSO2). Oxygen cascade and metabolism were monitored with arterial/venous blood gas analysis [arterial partial pressure of oxygen (PaO2), arterial saturation of oxygen (SaO2), oxygen delivery (DO2), and lactate], and IC [energy expenditure (REE), respiratory quotient (RQ), oxygen consumption (VO2), and carbon dioxide production (VCO2)]. Data were measured at PEEP 5 cmH2O and 15 cmH2O and expressed as delta (Δ) values. Ten patients with ABI [median age 70 (IQR 62-75) years, 6 (60%) were male, median Glasgow Coma Scale at ICU admission 5.5 (IQR 3-8)] were included. PEEP augmentation from 5 to 15 cmH2O did not affect cerebral oxygenation, systemic oxygen cascade parameters, and metabolism. The arterial component of cerebral oxygenation was significantly correlated with DO2 (ΔO2HBi, rho = 0.717, p = 0.037). ΔrSO2 (rho = 0.727, p = 0.032), ΔcHbi (rho = 0.797, p = 0.013), and ΔHHBi (rho = 0.816, p = 0.009) were significantly correlated with SaO2, but not ΔO2Hbi. ΔrSO2 was significantly correlated with VCO2 (rho = 0.681, p = 0.049). No correlation between brain oxygenation and ventilatory parameters was found. PEEP augmentation test did not affect cerebral and systemic oxygenation or metabolism. Changes in cerebral oxygenation significantly correlated with DO2, SaO2, and VCO2. Cerebral oxygen monitoring could be considered for individualization of mechanical ventilation setting in ABI patients without high or instable intracranial pressure.

Preload Responsiveness in Patients With Acute Respiratory Distress Syndrome Managed With Extracorporeal Membrane Oxygenation.

A restrictive fluid strategy is recommended in patients with acute respiratory distress syndrome (ARDS) managed with venovenous extracorporeal membrane oxygenation (VV ECMO). However, there are no established predictors for preload responsiveness in these patients. In 20 ARDS patients managed with VV ECMO, transesophageal echocardiography was used to repeatedly evaluate dynamic parameters of the left (velocity and stroke volume variation) and right ventricular outflow tract (velocity [respiratory variations of the maximal Doppler velocity in the truncus pulmonalis {ΔV max TP}] and velocity time integral [respiratory variation of the velocity time integral measured in the truncus pulmonalis {ΔVTI_TP}] variation in the truncus pulmonalis), the diameter variation in the superior and inferior vena cava and stroke volume variation measured by pulse contour analysis (SVV_PCA). Patients were categorized as responders and nonresponders according to an increase in stroke volume measured by echocardiography during a Passive Leg Raise Test with a cutoff value ≥10%. The final analysis includes 86 measurements. Predictive values for preload responsiveness were found for ΔV max TP (area under the curve [AUC] of 0.64), ΔVTI_TP (AUC 0.67), and SVV_PCA (AUC 0.74). In conclusion, SVV_PCA and, to a lesser extent, ΔV max TP and ΔVTI_TP are the most accurate parameters to predict preload responsiveness in ARDS patients managed with VV ECMO. Transesophageal echocardiography offers no advantages over pulse contour analysis for predicting preload responsiveness and provides only intermittent monitoring and assessment.

Dexmedetomidine improves pulmonary outcomes in thoracic surgery under one-lung ventilation: A meta-analysis.

INTRODUCTION: Dexmedetomidine improves intrapulmonary shunt in thoracic surgery and minimizes inflammatory response during one-lung ventilation (OLV). However, it is unclear whether such benefits translate into less postoperative pulmonary complications (PPCs). Our objective was to determine the impact of dexmedetomidine on the incidence of PPCs after thoracic surgery. METHODS: Major databases were used to identify randomized trials that compared dexmedetomidine versus placebo during thoracic surgery in terms of PPCs. Our primary outcome was atelectasis within 7 days after surgery. Other specific PPCs included hypoxemia, pneumonia, and acute respiratory distress syndrome (ARDS). Secondary outcome included intraoperative respiratory mechanics (respiratory compliance [Cdyn]) and postoperative lung function (forced expiratory volume [FEV1]). Random effects models were used to estimate odds ratios (OR). RESULTS: Twelve randomized trials, including 365 patients in the dexmedetomidine group and 359 in the placebo group, were analyzed in this meta-analysis. Patients in the dexmedetomidine group were less likely to develop postoperative atelectasis (2.3% vs 6.8%, OR 0.42, 95%CI 0.18-0.95, P = 0.04; low certainty) and hypoxemia (3.4% vs 11.7%, OR 0.26, 95%CI 0.10-0.68, P = 0.01; moderate certainty) compared to the placebo group. The incidence of postoperative pneumonia (3.2% vs 5.8%, OR 0.57, 95%CI 0.25-1.26, P = 0.17; moderate certainty) or ARDS (0.9% vs 3.5%, OR 0.39, 95%CI 0.07-2.08, P = 0.27; moderate certainty) was comparable between groups. Both intraoperative Cdyn and postoperative FEV1 were higher among patients that received dexmedetomidine with a mean difference of 4.42 mL/cmH2O (95%CI 3.13-5.72) and 0.27 L (95%CI 0.12-0.41), respectively. CONCLUSION: Dexmedetomidine administration during thoracic surgery may potentially reduce the risk of postoperative atelectasis and hypoxemia. However, current evidence is insufficient to demonstrate an effect on pneumonia or ARDS.

Hypothermia vs Normothermia in Patients With Cardiac Arrest and Nonshockable Rhythm: A Meta-Analysis.

Importance: International guidelines recommend body temperature control below 37.8 °C in unconscious patients with out-of-hospital cardiac arrest (OHCA); however, a target temperature of 33 °C might lead to better outcomes when the initial rhythm is nonshockable. Objective: To assess whether hypothermia at 33 °C increases survival and improves function when compared with controlled normothermia in unconscious adults resuscitated from OHCA with initial nonshockable rhythm. Data Sources: Individual patient data meta-analysis of 2 multicenter, randomized clinical trials (Targeted Normothermia after Out-of-Hospital Cardiac Arrest [TTM2; NCT02908308] and HYPERION [NCT01994772]) with blinded outcome assessors. Unconscious patients with OHCA and an initial nonshockable rhythm were eligible for the final analysis. Study Selection: The study cohorts had similar inclusion and exclusion criteria. Patients were randomized to hypothermia (target temperature 33 °C) or normothermia (target temperature 36.5 to 37.7 °C), according to different study protocols, for at least 24 hours. Additional analyses of mortality and unfavorable functional outcome were performed according to age, sex, initial rhythm, presence or absence of shock on admission, time to return of spontaneous circulation, lactate levels on admission, and the cardiac arrest hospital prognosis score. Data Extraction and Synthesis: Only patients who experienced OHCA and had a nonshockable rhythm with all causes of cardiac arrest were included. Variables from the 2 studies were available from the original data sets and pooled into a unique database and analyzed. Clinical outcomes were harmonized into a single file, which was checked for accuracy of numbers, distributions, and categories. The last day of follow-up from arrest was recorded for each patient. Adjustment for primary outcome and functional outcome was performed using age, gender, time to return of spontaneous circulation, and bystander cardiopulmonary resuscitation. Main Outcomes and Measures: The primary outcome was mortality at 3 months; secondary outcomes included unfavorable functional outcome at 3 to 6 months, defined as a Cerebral Performance Category score of 3 to 5. Results: A total of 912 patients were included, 490 from the TTM2 trial and 422 from the HYPERION trial. Of those, 442 had been assigned to hypothermia (48.4%; mean age, 65.5 years; 287 males [64.9%]) and 470 to normothermia (51.6%; mean age, 65.6 years; 327 males [69.6%]); 571 patients had a first monitored rhythm of asystole (62.6%) and 503 a presumed noncardiac cause of arrest (55.2%). At 3 months, 354 of 442 patients in the hypothermia group (80.1%) and 386 of 470 patients in the normothermia group (82.1%) had died (relative risk [RR] with hypothermia, 1.04; 95% CI, 0.89-1.20; P = .63). On the last day of follow-up, 386 of 429 in the hypothermia group (90.0%) and 413 of 463 in the normothermia group (89.2%) had an unfavorable functional outcome (RR with hypothermia, 0.99; 95% CI, 0.87-1.15; P = .97). The association of hypothermia with death and functional outcome was consistent across the prespecified subgroups. Conclusions and Relevance: In this individual patient data meta-analysis, including unconscious survivors from OHCA with an initial nonshockable rhythm, hypothermia at 33 °C did not significantly improve survival or functional outcome.

Effects of different positive end-expiratory pressure titration strategies on mechanical power during ultraprotective ventilation in ARDS patients treated with veno-venous extracorporeal membrane oxygenation: A prospective interventional study.

PURPOSE: Ultraprotective ventilation in acute respiratory distress syndrome (ARDS) patients with veno-venous extracorporeal membrane oxygenation (VV ECMO) reduces mechanical power (MP) through changes in positive end-expiratory pressure (PEEP); however, the optimal approach to titrate PEEP is unknown. This study assesses the effects of three PEEP titration strategies on MP, hemodynamic parameters, and oxygen delivery in twenty ARDS patients with VV ECMO. MATERIAL AND METHODS: PEEP was titrated according to: (A) a PEEP of 10 cmH2O representing the lowest recommendation by the Extracorporeal Life Support Organization (PEEPELSO), (B) the highest static compliance of the respiratory system (PEEPCstat,RS), and (C) a target end-expiratory transpulmonary pressure of 0 cmH2O (PEEPPtpexp). RESULTS: PEEPELSO was lower compared to PEEPCstat,RS and PEEPPtpexp (10.0 ± 0.0 vs. 16.2 ± 4.7 cmH2O and 17.3 ± 4.0 cmH2O, p < 0.001 each, respectively). PEEPELSO reduced MP compared to PEEPCstat,RS and PEEPPtpexp (5.3 ± 1.3 vs. 6.8 ± 2.0 and 6.9 ± 2.3 J/min, p < 0.001 each, respectively). PEEPELSO resulted in less lung stress compared to PEEPCstat,RS (p = 0.011) and PEEPPtpexp (p < 0.001) and increased cardiac output and oxygen delivery (p < 0.001 each). CONCLUSIONS: An empirical PEEP of 10 cmH2O minimized MP, provided favorable hemodynamics, and increased oxygen delivery in ARDS patients treated with VV ECMO. TRIAL REGISTRATION: German Clinical Trials Register (DRKS00013967). Registered 02/09/2018https://drks.de/search/en/trial/DRKS00013967.

Respiratory mechanics and mechanical power during low vs. high positive end-expiratory pressure in obese surgical patients - A sub-study of the PROBESE randomized controlled trial.

STUDY OBJECTIVE: We aimed to characterize intra-operative mechanical ventilation with low or high positive end-expiratory pressure (PEEP) and recruitment manoeuvres (RM) regarding intra-tidal recruitment/derecruitment and overdistension using non-linear respiratory mechanics, and mechanical power in obese surgical patients enrolled in the PROBESE trial. DESIGN: Prospective, two-centre substudy of the international, multicentre, two-arm, randomized-controlled PROBESE trial. SETTING: Operating rooms of two European University Hospitals. PATIENTS: Forty-eight adult obese patients undergoing abdominal surgery. INTERVENTIONS: Intra-operative protective ventilation with either PEEP of 12 cmH2O and repeated RM (HighPEEP+RM) or 4 cmH2O without RM (LowPEEP). MEASUREMENTS: The index of intra-tidal recruitment/de-recruitment and overdistension (%E2) as well as airway pressure, tidal volume (VT), respiratory rate (RR), resistance, elastance, and mechanical power (MP) were calculated from respiratory signals recorded after anesthesia induction, 1 h thereafter, and end of surgery (EOS). MAIN RESULTS: Twenty-four patients were analyzed in each group. PEEP was higher (mean ± SD, 11.7 ± 0.4 vs. 3.7 ± 0.6 cmH2O, P < 0.001) and driving pressure lower (12.8 ± 3.5 vs. 21.7 ± 6.8 cmH2O, P < 0.001) during HighPEEP+RM than LowPEEP, while VT and RR did not differ significantly (7.3 ± 0.6 vs. 7.4 ± 0.8 ml∙kg-1, P = 0.835; and 14.6 ± 2.5 vs. 15.7 ± 2.0 min-1, P = 0.150, respectively). %E2 was higher in HighPEEP+RM than in LowPEEP following induction (-3.1 ± 7.2 vs. -12.4 ± 10.2%; P < 0.001) and subsequent timepoints. Total resistance and elastance (13.3 ± 3.8 vs. 17.7 ± 6.8 cmH2O∙l∙s-2, P = 0.009; and 15.7 ± 5.5 vs. 28.5 ± 8.4 cmH2O∙l, P < 0.001, respectively) were lower during HighPEEP+RM than LowPEEP. Additionally, MP was lower in HighPEEP+RM than LowPEEP group (5.0 ± 2.2 vs. 10.4 ± 4.7 J∙min-1, P < 0.001). CONCLUSIONS: In this sub-cohort of PROBESE, intra-operative ventilation with high PEEP and RM reduced intra-tidal recruitment/de-recruitment as well as driving pressure, elastance, resistance, and mechanical power, as compared with low PEEP. TRIAL REGISTRATION: The PROBESE study was registered at www. CLINICALTRIALS: gov, identifier: NCT02148692 (submission for registration on May 23, 2014).

Impact of withholding early antibiotic therapy in nonseptic surgical patients with suspected nosocomial infection: a retrospective cohort analysis

Abstract Background: Systemic inflammatory responses mimicking infectious complications are often present in surgical patients. Methods: The objective was to assess the association between withholding early antimicrobial therapy while investigating alternative diagnoses and worse outcomes in nonseptic patients with suspected nosocomial infection in a retrospective cohort of critically ill surgical patients. The initiation of antibiotic therapy within 24 h of the suspicion of infection was defined as the Early Empirical Antibiotic strategy (EEA) group and the initiation after 24 h of suspicion or not prescribed was defined as the Conservative Antibiotic strategy (CA) group. Primary outcome was composite: death, sepsis, or septic shock within 14 days. Main exclusion criteria were sepsis or an evident source of infection at inclusion. Results: Three hundred and forty patients were eligible for inclusion (74% trauma patients). Age, sex, reason for hospital admission, SAPS3 score, SOFA score, and use of vasopressors or mechanical ventilation were not different between the groups. Within 14 days of inclusion, 100% (130/130) of EEA patients received antibiotics compared to 57% (120/210) of CA patients. After adjusting for confounding variables, there was no association between primary outcome and the groups. In a post hoc subgroup analysis including only patients with a posteriori confirmed infection (by microbiological cultures), delay in initiation of adequate antimicrobial therapy was independently associated with the primary outcome (Odds Ratio = 1.19 per day of delay; 95% CI 1.05-1.37). Conclusions: Withholding early empiric antibiotic therapy was not associated with progression of organ dysfunction within 14 days in nonseptic surgical patients with suspected nosocomial infection without an obvious source.

Pressure-support compared with pressure-controlled ventilation mitigates lung and brain injury in experimental acute ischemic stroke in rats.

BACKGROUND: We aimed to evaluate the pulmonary and cerebral effects of low-tidal volume ventilation in pressure-support (PSV) and pressure-controlled (PCV) modes at two PEEP levels in acute ischemic stroke (AIS). METHODS: In this randomized experimental study, AIS was induced by thermocoagulation in 30 healthy male Wistar rats. After 24 h, AIS animals were randomly assigned to PSV or PCV with VT = 6 mL/kg and PEEP = 2 cmH2O (PSV-PEEP2 and PCV-PEEP2) or PEEP = 5 cmH2O (PSV-PEEP5 and PCV-PEEP5) for 2 h. Lung mechanics, arterial blood gases, and echocardiography were evaluated before and after the experiment. Lungs and brain tissue were removed for histologic and molecular biology analysis. The primary endpoint was diffuse alveolar damage (DAD) score; secondary endpoints included brain histology and brain and lung molecular biology markers. RESULTS: In lungs, DAD was lower with PSV-PEEP5 than PCV-PEEP5 (p < 0.001); interleukin (IL)-1ß was lower with PSV-PEEP2 than PCV-PEEP2 (p = 0.016) and PSV-PEEP5 than PCV-PEEP5 (p = 0.046); zonula occludens-1 (ZO-1) was lower in PCV-PEEP5 than PCV-PEEP2 (p = 0.042). In brain, necrosis, hemorrhage, neuropil edema, and CD45 + microglia were lower in PSV than PCV animals at PEEP = 2 cmH2O (p = 0.036, p = 0.025, p = 0.018, p = 0.011, respectively) and PEEP = 5 cmH2O (p = 0.003, p = 0.003, p = 0.007, p = 0.003, respectively); IL-1ß was lower while ZO-1 was higher in PSV-PEEP2 than PCV-PEEP2 (p = 0.009, p = 0.007, respectively), suggesting blood-brain barrier integrity. Claudin-5 was higher in PSV-PEEP2 than PSV-PEEP5 (p = 0.036). CONCLUSION: In experimental AIS, PSV compared with PCV reduced lung and brain injury. Lung ZO-1 reduced in PCV with PEEP = 2 versus PEEP = 5 cmH2O, while brain claudin-5 increased in PSV with PEEP = 2 versus PEEP = 5 cmH2O.