High Mechanical Power and Driving Pressures are Associated With Postoperative Respiratory Failure Independent From Patients' Respiratory System Mechanics.

OBJECTIVES: High mechanical power and driving pressure (ΔP) have been associated with postoperative respiratory failure (PRF) and may be important parameters guiding mechanical ventilation. However, it remains unclear whether high mechanical power and ΔP merely reflect patients with poor respiratory system mechanics at risk of PRF. We investigated the effect of mechanical power and ΔP on PRF in cohorts after exact matching by patients' baseline respiratory system compliance. DESIGN: Hospital registry study. SETTING: Academic hospital in New England. PATIENTS: Adult patients undergoing general anesthesia between 2008 and 2020. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: The primary exposure was high (≥ 6.7 J/min, cohort median) versus low mechanical power and the key-secondary exposure was high (≥ 15.0 cm H 2 O) versus low ΔP. The primary endpoint was PRF (reintubation or unplanned noninvasive ventilation within seven days). Among 97,555 included patients, 4,030 (4.1%) developed PRF. In adjusted analyses, high intraoperative mechanical power and ΔP were associated with higher odds of PRF (adjusted odds ratio [aOR] 1.37 [95% CI, 1.25-1.50]; p < 0.001 and aOR 1.45 [95% CI, 1.31-1.60]; p < 0.001, respectively). There was large variability in applied ventilatory parameters, dependent on the anesthesia provider. This facilitated matching of 63,612 (mechanical power cohort) and 53,260 (ΔP cohort) patients, yielding identical baseline standardized respiratory system compliance (standardized difference [SDiff] = 0.00) with distinctly different mechanical power (9.4 [2.4] vs 4.9 [1.3] J/min; SDiff = -2.33) and ΔP (19.3 [4.1] vs 11.9 [2.1] cm H 2 O; SDiff = -2.27). After matching, high mechanical power and ΔP remained associated with higher risk of PRF (aOR 1.30 [95% CI, 1.17-1.45]; p < 0.001 and aOR 1.28 [95% CI, 1.12-1.46]; p < 0.001, respectively). CONCLUSIONS: High mechanical power and ΔP are associated with PRF independent of patient's baseline respiratory system compliance. Our findings support utilization of these parameters for titrating mechanical ventilation in the operating room and ICU.

Mechanically Ventilated Patients With Coronavirus Disease 2019 Had a Higher Chance of In-Hospital Death If Treated With High-Flow Nasal Cannula Oxygen Before Intubation.

BACKGROUND: The impact of high-flow nasal cannula (HFNC) on outcomes of patients with respiratory failure from coronavirus disease 2019 (COVID-19) is unknown. We sought to assess whether exposure to HFNC before intubation was associated with successful extubation and in-hospital mortality compared to patients receiving intubation only. METHODS: This single-center retrospective study examined patients with COVID-19-related respiratory failure from March 2020 to March 2021 who required HFNC, intubation, or both. Data were abstracted from the electronic health record. Use and duration of HFNC and intubation were examined' as well as demographics and clinical characteristics. We assessed the association between HFNC before intubation (versus without) and chance of successful extubation and in-hospital death using Cox proportional hazards models adjusting for age, sex, race/ethnicity, obesity, hypertension, diabetes, prior chronic obstructive pulmonary disease or asthma, HCO 3 , CO 2 , oxygen-saturation-to-inspired-oxygen (S:F) ratio, pulse, respiratory rate, temperature, and length of stay before intervention. RESULTS: A total of n = 440 patients were identified, of whom 311 (70.7%) received HFNC before intubation, and 129 (29.3%) were intubated without prior use of HFNC. Patients who received HFNC before intubation had a higher chance of in-hospital death (hazard ratio [HR], 2.08; 95% confidence interval [CI], 1.06-4.05). No difference was found in the chance of successful extubation between the 2 groups (0.70, 0.41-1.20). CONCLUSIONS: Among patients with respiratory failure from COVID-19 requiring mechanical ventilation, patients receiving HFNC before intubation had a higher chance of in-hospital death. Decisions on initial respiratory support modality should weigh the risks of intubation with potential increased mortality associated with HFNC.

Reverse Trigger Phenotypes in Acute Respiratory Distress Syndrome.

Rationale: Reverse triggering is an underexplored form of dyssynchrony with important clinical implications in patients with acute respiratory distress syndrome.Objectives: This retrospective study identified reverse trigger phenotypes and characterized their impacts on Vt and transpulmonary pressure.Methods: Fifty-five patients with acute respiratory distress syndrome on pressure-regulated ventilator modes were included. Four phenotypes of reverse triggering with and without breath stacking and their impact on lung inflation and deflation were investigated.Measurements and Main Results: Inflation volumes, respiratory muscle pressure generation, and transpulmonary pressures were determined and phenotypes differentiated using Campbell diagrams of respiratory activity. Reverse triggering was detected in 25 patients, 15 with associated breath stacking, and 13 with stable reverse triggering consistent with respiratory entrainment. Phenotypes were associated with variable levels of inspiratory effort (mean 4-10 cm H2O per phenotype). Early reverse triggering with early expiratory relaxation increased Vts (88 [64-113] ml) and inspiratory transpulmonary pressures (3 [2-3] cm H2O) compared with passive breaths. Early reverse triggering with delayed expiratory relaxation increased Vts (128 [86-170] ml) and increased inspiratory and mean-expiratory transpulmonary pressure (7 [5-9] cm H2O and 5 [4-6] cm H2O). Mid-cycle reverse triggering (initiation during inflation and maximal effort during deflation) increased Vt (51 [38-64] ml), increased inspiratory and mean-expiratory transpulmonary pressure (3 [2-4] cm H2O and 3 [2-3] cm H2O), and caused incomplete exhalation. Late reverse triggering (occurring exclusively during exhalation) increased mean expiratory transpulmonary pressure (2 [1-2] cm H2O) and caused incomplete exhalation. Breath stacking resulted in large delivered volumes (176 [155-197] ml).Conclusions: Reverse triggering causes variable physiological effects, depending on the phenotype. Differentiation of phenotype effects may be important to understand the clinical impacts of these events.

Anesthetics to Prevent Lung Injury in Cardiac Surgery: A Randomized Controlled Trial.

OBJECTIVES: To investigate if sevoflurane based anesthesia is superior to propofol in preventing lung inflammation and preventing postoperative pulmonary complications. DESIGN: Randomized controlled trial. SETTING: Single tertiary care university hospital. PARTICIPANTS: Forty adults undergoing cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: Patients were randomized in a 1:1 ratio to anesthetic maintenance with sevoflurane or propofol. MEASUREMENTS AND MAIN RESULTS: Blood and bronchoalveolar lavage fluid was sampled before and after bypass to measure pulmonary inflammation using a biomarker panel. The change in bronchoalveolar lavage concentration of tumor necrosis factor alpha (TNFα) was the primary outcome. Secondary outcomes included lung inflammation defined as changes in other biomarkers and postoperative pulmonary complications. There were no significant differences between groups in the change in bronchoalveolar lavage TNFα concentration (median [IQR] change, 17.24 [1.11-536.77] v 101.51 [1.47-402.84] pg/mL, sevoflurane v propofol, p = 0.31). There was a significantly lower postbypass concentration of plasma interleukin 8 (median [IQR], 53.92 [34.5-55.91] v 66.92 [53.03-94.44] pg/mL, p = 0.04) and a significantly smaller postbypass increase in the plasma receptor for advanced glycosylation end products (median [IQR], 174.59 [73.59-446.06] v 548.22 [193.15-852.39] pg/mL, p = 0.03) in the sevoflurane group compared with propofol. The incidence of postoperative pulmonary complications was 100% in both groups, with high rates of pleural effusion (17/18 [94.44%] v 19/22 [86.36%], p = 0.39) and hypoxemia (16/18 [88.88%] v 22/22 [100%], p = 0.11). CONCLUSIONS: Sevoflurane anesthesia during cardiac surgery did not consistently prevent lung inflammation or prevent postoperative pulmonary complications compared to propofol. There were significantly lower levels of 2 plasma biomarkers specific for lung injury and inflammation in the sevoflurane group.

Intraoperative Oxygen Concentration and Neurocognition after Cardiac Surgery.

BACKGROUND: Despite evidence suggesting detrimental effects of perioperative hyperoxia, hyperoxygenation remains commonplace in cardiac surgery. Hyperoxygenation may increase oxidative damage and neuronal injury leading to potential differences in postoperative neurocognition. Therefore, this study tested the primary hypothesis that intraoperative normoxia, as compared to hyperoxia, reduces postoperative cognitive dysfunction in older patients having cardiac surgery. METHODS: A randomized double-blind trial was conducted in patients aged 65 yr or older having coronary artery bypass graft surgery with cardiopulmonary bypass. A total of 100 patients were randomized to one of two intraoperative oxygen delivery strategies. Normoxic patients (n = 50) received a minimum fraction of inspired oxygen of 0.35 to maintain a Pao2 above 70 mmHg before and after cardiopulmonary bypass and between 100 and 150 mmHg during cardiopulmonary bypass. Hyperoxic patients (n = 50) received a fraction of inspired oxygen of 1.0 throughout surgery, irrespective of Pao2 levels. The primary outcome was neurocognitive function measured on postoperative day 2 using the Telephonic Montreal Cognitive Assessment. Secondary outcomes included neurocognitive function at 1, 3, and 6 months, as well as postoperative delirium, mortality, and durations of mechanical ventilation, intensive care unit stay, and hospital stay. RESULTS: The median age was 71 yr (interquartile range, 68 to 75), and the median baseline neurocognitive score was 17 (16 to 19). The median intraoperative Pao2 was 309 (285 to 352) mmHg in the hyperoxia group and 153 (133 to 168) mmHg in the normoxia group (P < 0.001). The median Telephonic Montreal Cognitive Assessment score on postoperative day 2 was 18 (16 to 20) in the hyperoxia group and 18 (14 to 20) in the normoxia group (P = 0.42). Neurocognitive function at 1, 3, and 6 months, as well as secondary outcomes, were not statistically different between groups. CONCLUSIONS: In this randomized controlled trial, intraoperative normoxia did not reduce postoperative cognitive dysfunction when compared to intraoperative hyperoxia in older patients having cardiac surgery. Although the optimal intraoperative oxygenation strategy remains uncertain, the results indicate that intraoperative hyperoxia does not worsen postoperative cognition after cardiac surgery.

Cost-Effectiveness Research in Anesthesiology.

Perioperative interventions aimed at decreasing costs and improving outcomes have become increasingly popular in recent years. Anesthesiologists are often faced with a choice among different treatment strategies with little data available on the comparative cost-effectiveness. We performed a systematic review of the English language literature between 1980 and 2014 to identify cost-effectiveness analyses of anesthesiology and perioperative medicine interventions. We excluded interventions related to critical care or pediatric anesthesiology, and articles on interventions not normally ordered or performed by anesthesiologists. Of the >5000 cost-effectiveness analyses published to date, only 28 were applicable to anesthesiology and perioperative medicine and met inclusion criteria. Multidisciplinary interventions were the most cost-effective overall; 8 of 8 interventions were "dominant" (improved outcomes, reduced cost) or cost-effective, including accelerated, standardized perioperative recovery pathways, and perioperative delirium prevention bundles. Intraoperative measures were dominant in 3 of 5 cases, including spinal anesthesia for benign abdominal hysterectomy. With regard to prevention of perioperative infection, methicillin-resistant Staphylococcus aureus (MRSA) decolonization was dominant or cost-effective in 2 of 2 studies. Three studies assessing various antibiotic prophylaxis regimens had mixed results. Autologous blood donation was not found to be cost-effective in 5 of 7 studies, and intraoperative cell salvage therapy was also not cost-effective in 2 of 2 reports. Overall, there remains a paucity of cost-effectiveness literature in anesthesiology, particularly relating to intraoperative interventions and multidisciplinary perioperative interventions. Based on the available studies, multidisciplinary perioperative optimization interventions such as accelerated, standardized perioperative recovery pathways, and perioperative delirium prevention bundles tended to be most cost-effective. Our review demonstrates that there is a need for more rigorous cost-effective analyses in many areas of anesthesiology and that anesthesiologists should continue to lead collaborative, multidisciplinary efforts in perioperative medicine.

Hospital Incidence and Outcomes of the Acute Respiratory Distress Syndrome Using the Kigali Modification of the Berlin Definition.

RATIONALE: Estimates of the incidence of the acute respiratory distress syndrome (ARDS) in high- and middle-income countries vary from 10.1 to 86.2 per 100,000 person-years in the general population. The epidemiology of ARDS has not been reported for a low-income country at the level of the population, hospital, or intensive care unit (ICU). The Berlin definition may not allow identification of ARDS in resource-constrained settings. OBJECTIVES: To estimate the incidence and outcomes of ARDS at a Rwandan referral hospital using the Kigali modification of the Berlin definition: without requirement for positive end-expiratory pressure, hypoxia cutoff of SpO2/FiO2 less than or equal to 315, and bilateral opacities on lung ultrasound or chest radiograph. METHODS: We screened every adult patient for hypoxia at a public referral hospital in Rwanda for 6 weeks. For every patient with hypoxia, we collected data on demographics and ARDS risk factors, performed lung ultrasonography, and evaluated chest radiography when available. MEASUREMENTS AND MAIN RESULTS: Forty-two (4.0%) of 1,046 hospital admissions met criteria for ARDS. Using various prespecified cutoffs for the SpO2/FiO2 ratio resulted in almost identical hospital incidence values. Median age for patients with ARDS was 37 years, and infection was the most common risk factor (44.1%). Only 30.9% of patients with ARDS were admitted to an ICU, and hospital mortality was 50.0%. Using traditional Berlin criteria, no patients would have met criteria for ARDS. CONCLUSIONS: ARDS seems to be a common and fatal syndrome in a hospital in Rwanda, with few patients admitted to an ICU. The Berlin definition is likely to underestimate the impact of ARDS in low-income countries, where resources to meet the definition requirements are lacking. Although the Kigali modification requires validation before widespread use, we hope this study stimulates further work in refining an ARDS definition that can be consistently used in all settings.

The Effect of Positive End-Expiratory Pressure on Intracranial Pressure and Cerebral Hemodynamics.

BACKGROUND: Lung protective ventilation has not been evaluated in patients with brain injury. It is unclear whether applying positive end-expiratory pressure (PEEP) adversely affects intracranial pressure (ICP) and cerebral perfusion pressure (CPP). We aimed to evaluate the effect of PEEP on ICP and CPP in a large population of patients with acute brain injury and varying categories of acute lung injury, defined by PaO2/FiO2. METHOD: Retrospective data were collected from 341 patients with severe acute brain injury admitted to the ICU between 2008 and 2015. These patients experienced a total of 28,644 paired PEEP and ICP observations. Demographic, hemodynamic, physiologic, and ventilator data at the time of the paired PEEP and ICP observations were recorded. RESULTS: In the adjusted analysis, a statistically significant relationship between PEEP and ICP and PEEP and CPP was found only among observations occurring during periods of severe lung injury. For every centimeter H2O increase in PEEP, there was a 0.31 mmHg increase in ICP (p = 0.04; 95 % CI [0.07, 0.54]) and a 0.85 mmHg decrease in CPP (p = 0.02; 95 % CI [-1.48, -0.22]). CONCLUSION: Our results suggest that PEEP can be applied safely in patients with acute brain injury as it does not have a clinically significant effect on ICP or CPP. Further prospective studies are required to assess the safety of applying a lung protective ventilation strategy in brain-injured patients with lung injury.

Controversies in the Management of Severe ARDS: Optimal Ventilator Management and Use of Rescue Therapies.

Groundbreaking research into the pathophysiology of the adult acute respiratory distress syndrome (ARDS) and the prevention of ventilator-induced lung injury has led to dramatic improvements in survival. Investigations over the last two decades have revolved around the development of rescue therapies that can be used for patients with severe ARDS and refractory hypoxemia. To date, the techniques of using high levels of positive end-expiratory pressure (PEEP), prompt institution of neuromuscular blockade, and early prolonged prone positioning have been shown to reduce mortality in patients with severe ARDS. PEEP titration using transpulmonary pressure estimations assisted by esophageal manometry has been shown to result in a substantial improvement in oxygenation. Extracorporeal membrane oxygenation (ECMO) has been used increasingly since the mid-2000s in part due to the H1N1 epidemic. A major randomized controlled trial conducted during this period showed a significant mortality benefit for patients with severe ARDS who were referred to a center with ECMO capabilities. The routine use of inhaled nitric oxide for patients with severe ARDS has not been shown to lead to more than a transient and limited improvement in oxygenation, which may hinder its use as a sole rescue therapy. Finally, recent studies have found that the routine use of high-frequency oscillatory ventilation in severe ARDS does not result in decreased mortality, although the technique has not been specifically investigated as rescue therapy for severe refractory hypoxemia.

Predicting risk of postoperative lung injury in high-risk surgical patients: a multicenter cohort study.

BACKGROUND: Acute respiratory distress syndrome (ARDS) remains a serious postoperative complication. Although ARDS prevention is a priority, the inability to identify patients at risk for ARDS remains a barrier to progress. The authors tested and refined the previously reported surgical lung injury prediction (SLIP) model in a multicenter cohort of at-risk surgical patients. METHODS: This is a secondary analysis of a multicenter, prospective cohort investigation evaluating high-risk patients undergoing surgery. Preoperative ARDS risk factors and risk modifiers were evaluated for inclusion in a parsimonious risk-prediction model. Multiple imputation and domain analysis were used to facilitate development of a refined model, designated SLIP-2. Area under the receiver operating characteristic curve and the Hosmer-Lemeshow goodness-of-fit test were used to assess model performance. RESULTS: Among 1,562 at-risk patients, ARDS developed in 117 (7.5%). Nine independent predictors of ARDS were identified: sepsis, high-risk aortic vascular surgery, high-risk cardiac surgery, emergency surgery, cirrhosis, admission location other than home, increased respiratory rate (20 to 29 and ≥30 breaths/min), FIO2 greater than 35%, and SpO2 less than 95%. The original SLIP score performed poorly in this heterogeneous cohort with baseline risk factors for ARDS (area under the receiver operating characteristic curve [95% CI], 0.56 [0.50 to 0.62]). In contrast, SLIP-2 score performed well (area under the receiver operating characteristic curve [95% CI], 0.84 [0.81 to 0.88]). Internal validation indicated similar discrimination, with an area under the receiver operating characteristic curve of 0.84. CONCLUSIONS: In this multicenter cohort of patients at risk for ARDS, the SLIP-2 score outperformed the original SLIP score. If validated in an independent sample, this tool may help identify surgical patients at high risk for ARDS.

Examining the Role of Race in End-of-Life Care in the Intensive Care Unit: A Single-Center Observational Study.

Background: Prior studies have shown variation in the intensity of end-of-life care in intensive care units (ICUs) among patients of different races. Objective: We sought to identify variation in the levels of care at the end of life in the ICU and to assess for any association with race and ethnicity. Design: An observational, retrospective cohort study. Settings: A tertiary care center in Boston, MA. Participants: All critically ill patients admitted to medical and surgical ICUs between June 2019 and December 2020. Exposure: Self-identified race and ethnicity. Main Outcome and Measure: The primary outcome was death. Secondary outcomes included "code status," markers of intensity of care, consultation by the Palliative care service, and consultation by the Ethics service. Results: A total of 9083 ICU patient encounters were analyzed. One thousand two hundred fifty-nine patients (14%) died in the ICU; the mean age of patients was 64 years (standard deviation 16.8), and 44% of patients were women. A large number of decedents (22.7%) did not have their race identified. These patients had a high rate of interventions at death. Code status varied by race, with more White patients designated as "Comfort Measures Only" (CMO) (74%) whereas more Black patients were designated as "Do Not Resuscitate/Do Not Intubate (DNR/DNI) and DNR/ok to intubate" (12.1% and 15.7%) at the end of life; after adjustment for age and severity of illness, there were no statistical differences by race for the use of the CMO code status. Use of dialysis at the end of life varied by self-identified race. Specifically, Black and Unknown patients were more likely to receive renal replacement therapy, even after adjustment for age and severity of illness (24% and 20%, p = 0.003). Conclusions: Our data describe a gap in identification of race and ethnicity, as well as differences at the end of life in the ICU, especially with respect to code status and certain markers of intensity.

MUlticenter STudy of tissue plasminogen activator (alteplase) use in COVID-19 severe respiratory failure (MUST COVID): A retrospective cohort study.

Background: Few therapies exist to treat severe COVID-19 respiratory failure once it develops. Given known diffuse pulmonary microthrombi on autopsy studies of COVID-19 patients, we hypothesized that tissue plasminogen activator (tPA) may improve pulmonary function in COVID-19 respiratory failure. Methods: A multicenter, retrospective, observational study of patients with confirmed COVID-19 and severe respiratory failure who received systemic tPA (alteplase) was performed. Seventy-nine adults from seven medical centers were included in the final analysis after institutional review boards' approval; 23 were excluded from analysis because tPA was administered for pulmonary macroembolism or deep venous thrombosis. The primary outcome was improvement in the PaO2/FiO2 ratio from baseline to 48 h after tPA. Linear mixed modeling was used for analysis. Results: tPA was associated with significant PaO2/FiO2 improvement at 48 h (estimated paired difference = 23.1 ± 6.7), which was sustained at 72 h (interaction term p < 0.00). tPA administration was also associated with improved National Early Warning Score 2 scores at 24, 48, and 72 h after receiving tPA (interaction term p = 0.00). D-dimer was significantly elevated immediately after tPA, consistent with lysis of formed clot. Patients with declining respiratory status preceding tPA administration had more marked improvement in PaO2/FiO2 ratios than those who had poor but stable (not declining) respiratory status. There was one intracranial hemorrhage, which occurred within 24 h following tPA administration. Conclusions: These data suggest tPA is associated with significant improvement in pulmonary function in severe COVID-19 respiratory failure, especially in patients whose pulmonary function is in decline, and has an acceptable safety profile in this patient population.

Study of Alteplase for Respiratory Failure in SARS-CoV-2 COVID-19: A Vanguard Multicenter, Rapidly Adaptive, Pragmatic, Randomized Controlled Trial.

BACKGROUND: Pulmonary vascular microthrombi are a proposed mechanism of COVID-19 respiratory failure. We hypothesized that early administration of tissue plasminogen activator (tPA) followed by therapeutic heparin would improve pulmonary function in these patients. RESEARCH QUESTION: Does tPA improve pulmonary function in severe COVID-19 respiratory failure, and is it safe? STUDY DESIGN AND METHODS: Adults with COVID-19-induced respiratory failure were randomized from May14, 2020 through March 3, 2021, in two phases. Phase 1 (n = 36) comprised a control group (standard-of-care treatment) vs a tPA bolus (50-mg tPA IV bolus followed by 7 days of heparin; goal activated partial thromboplastin time [aPTT], 60-80 s) group. Phase 2 (n = 14) comprised a control group vs a tPA drip (50-mg tPA IV bolus, followed by tPA drip 2 mg/h plus heparin 500 units/h over 24 h, then heparin to maintain aPTT of 60-80 s for 7 days) group. Patients were excluded from enrollment if they had not undergone a neurologic examination or cross-sectional brain imaging within the previous 4.5 h to rule out stroke and potential for hemorrhagic conversion. The primary outcome was Pao2 to Fio2 ratio improvement from baseline at 48 h after randomization. Secondary outcomes included Pao2 to Fio2 ratio improvement of > 50% or Pao2 to Fio2 ratio of ≥ 200 at 48 h (composite outcome), ventilator-free days (VFD), and mortality. RESULTS: Fifty patients were randomized: 17 in the control group and 19 in the tPA bolus group in phase 1 and eight in the control group and six in the tPA drip group in phase 2. No severe bleeding events occurred. In the tPA bolus group, the Pao2 to Fio2 ratio values were significantly (P < .017) higher than baseline at 6 through 168 h after randomization; the control group showed no significant improvements. Among patients receiving a tPA bolus, the percent change of Pao2 to Fio2 ratio at 48 h (16.9% control [interquartile range (IQR), -8.3% to 36.8%] vs 29.8% tPA bolus [IQR, 4.5%-88.7%]; P = .11), the composite outcome (11.8% vs 47.4%; P = .03), VFD (0.0 [IQR, 0.0-9.0] vs 12.0 [IQR, 0.0-19.0]; P = .11), and in-hospital mortality (41.2% vs 21.1%; P = .19) did not reach statistically significant differences when compared with those of control participants. The patients who received a tPA drip did not experience benefit. INTERPRETATION: The combination of tPA bolus plus heparin is safe in severe COVID-19 respiratory failure. A phase 3 study is warranted given the improvements in oxygenation and promising observations in VFD and mortality. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT04357730; URL: www. CLINICALTRIALS: gov.

Association of prehospitalization aspirin therapy and acute lung injury: results of a multicenter international observational study of at-risk patients.

OBJECTIVE: To evaluate the association between prehospitalization aspirin therapy and incident acute lung injury in a heterogeneous cohort of at-risk medical patients. DESIGN: This is a secondary analysis of a prospective multicenter international cohort investigation. SETTING: Multicenter observational study including 20 US hospitals and two hospitals in Turkey. PATIENTS: Consecutive, adult, nonsurgical patients admitted to the hospital with at least one major risk factor for acute lung injury. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Baseline characteristics and acute lung injury risk factors/modifiers were identified. The presence of aspirin therapy and the propensity to receive this therapy were determined. The primary outcome was acute lung injury during hospitalization. Secondary outcomes included intensive care unit and hospital mortality and intensive care unit and hospital length of stay. Twenty-two hospitals enrolled 3855 at-risk patients over a 6-month period. Nine hundred seventy-six (25.3%) were receiving aspirin at the time of hospitalization. Two hundred forty (6.2%) patients developed acute lung injury. Univariate analysis noted a reduced incidence of acute lung injury in those receiving aspirin therapy (odds ratio [OR], 0.65; 95% confidence interval [CI], 0.46-0.90; p = .010). This association was attenuated in a stratified analysis based on deciles of aspirin propensity scores (Cochran-Mantel-Haenszel pooled OR, 0.70; 95% CI, 0.48-1.03; p = .072). CONCLUSIONS: After adjusting for the propensity to receive aspirin therapy, no statistically significant associations between prehospitalization aspirin therapy and acute lung injury were identified; however, a prospective clinical trial to further evaluate this association appears warranted.

Predicting mortality in adults with suspected infection in a Rwandan hospital: an evaluation of the adapted MEWS, qSOFA and UVA scores.

RATIONALE: Mortality prediction scores are increasingly being evaluated in low and middle income countries (LMICs) for research comparisons, quality improvement and clinical decision-making. The modified early warning score (MEWS), quick Sequential (Sepsis-Related) Organ Failure Assessment (qSOFA), and Universal Vital Assessment (UVA) score use variables that are feasible to obtain, and have demonstrated potential to predict mortality in LMIC cohorts. OBJECTIVE: To determine the predictive capacity of adapted MEWS, qSOFA and UVA in a Rwandan hospital. DESIGN, SETTING, PARTICIPANTS AND OUTCOME MEASURES: We prospectively collected data on all adult patients admitted to a tertiary hospital in Rwanda with suspected infection over 7 months. We calculated an adapted MEWS, qSOFA and UVA score for each participant. The predictive capacity of each score was assessed including sensitivity, specificity, positive and negative predictive value, OR, area under the receiver operating curve (AUROC) and performance by underlying risk quartile. RESULTS: We screened 19 178 patient days, and enrolled 647 unique patients. Median age was 35 years, and in-hospital mortality was 18.1%. The proportion of data missing for each variable ranged from 0% to 11.7%. The sensitivities and specificities of the scores were: adapted MEWS >4, 50.4% and 74.9%, respectively; qSOFA >2, 24.8% and 90.4%, respectively; and UVA >4, 28.2% and 91.1%, respectively. The scores as continuous variables demonstrated the following AUROCs: adapted MEWS 0.69 (95% CI 0.64 to 0.74), qSOFA 0.65 (95% CI 0.60 to 0.70), and UVA 0.71 (95% CI 0.66 to 0.76); there was no statistically significant difference between the discriminative capacities of the scores. CONCLUSION: Three scores demonstrated a modest ability to predict mortality in a prospective study of inpatients with suspected infection at a Rwandan tertiary hospital. Careful consideration must be given to their adequacy before using them in research comparisons, quality improvement or clinical decision-making.

Recall of clinical trial participation and attrition rates in survivors of acute respiratory distress syndrome.

PURPOSE: To measure the rate of recall of study participation and study attrition in survivors of acute respiratory distress syndrome(ARDS). MATERIALS/METHODS: In this ancillary study of the Re-evaluation of Systemic Early neuromuscular blockade(ROSE) trial, we measured the rate of study participation recall 3 months following discharge and subsequent study attrition at 6 months. We compared patient and hospital characteristics, and long-term outcomes by recall. As surrogate decision-makers provided initial consent, we measured the rate of patient reconsent and its association with study recall. RESULTS: Of 487 patients evaluated, recall status was determined in 386(82.7%). Among these, 287(74.4%) patients recalled participation in the ROSE trial, while 99(25.6%) did not. There was no significant difference in 6-month attrition among patients who recalled study participation (9.1%) and those who did not (12.1%) (p = 0.38). Patient characteristics were similar between groups, except SOFA scores, ventilator-free days, and length of stay. 330(68%) were reconsented. Compared to those not reconsented, significantly more patients who were reconsented recalled study participation(78% vs. 66%;p = 0.01). CONCLUSIONS: One in 4 ARDS survivors do not recall their participation in a clinical trial during hospitalization 3 months following hospital discharge, which did not influence 6-month attrition. However, more patients recall study participation if reconsent is obtained.

Effect of Early High-Dose Vitamin D3 Repletion on Cognitive Outcomes in Critically Ill Adults.

BACKGROUND: Long-term cognitive impairment frequently occurs after critical illness; no treatments are known to improve long-term cognition. RESEARCH QUESTION: Does a single high-dose (540,000 International Units) enteral treatment of vitamin D3 given shortly after hospital admission in critically ill patients who are vitamin D deficient improve long-term global cognition or executive function? STUDY DESIGN AND METHODS: This study evaluated long-term cognitive outcomes among patients enrolled in a multicenter, blinded, randomized clinical trial comparing vitamin D3 treatment vs placebo in critically ill adults with vitamin D deficiency. Global cognition was measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Executive function was measured with a composite score derived from three Delis-Kaplan Executive Function System subscales. Outcomes were assessed at a median of 443 days (interquartile range, 390-482 days) after randomization and were compared using multivariate proportional odds regression. Adjusted ORs of > 1.0 would indicate better outcomes in the vitamin D3 group compared with the placebo group. RESULTS: Ninety-five patients were enrolled, including 47 patients randomized to vitamin D3 treatment and 48 patients randomized to placebo. The adjusted median RBANS score at follow-up was 79.6 (95% CI, 73.0-84.0) in the vitamin D3 group and 82.1 (95% CI, 74.7-84.6) in the placebo group (adjusted OR, 0.83; 95% CI, 0.50-1.38). The adjusted median executive function composite scores were 8.1 (95% CI, 6.8-9.0) and 8.7 (95% CI, 7.4-9.3), respectively (adjusted OR, 0.72; 95% CI, 0.36-1.42). INTERPRETATION: In vitamin D-deficient, critically-ill adults, a large dose of enteral vitamin D3 did not improve long-term global cognition or executive function. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03733418; URL: www.clinicaltrials.gov.

Should prone positioning be routinely used for lung protection during mechanical ventilation?

Prone positioning has been known for decades to improve oxygenation in animals with acute lung injury and in most patients with acute respiratory distress syndrome (ARDS). The mechanisms of this improvement include a more uniform pleural-pressure gradient, a smaller volume of lung compressed by the heart, and more uniform and better-matched ventilation and perfusion. Prone positioning has an established niche as an intervention to improve gas exchange in patients with severe hypoxemia refractory to standard ventilatory manipulations. Because the lung may be more uniformly recruited and the stress of mechanical ventilation better distributed, prone positioning has also been proposed as a form of lung-protective ventilation. However, several randomized trials have failed to show improvements in clinical outcomes of ARDS patients, other than consistently better oxygenation. Because each of these trials had design problems or early termination, prone positioning remains a rescue therapy for patients with acute lung injury or ARDS.

Are esophageal pressure measurements important in clinical decision-making in mechanically ventilated patients?

Low-tidal-volume ventilation strategies are clearly beneficial in patients with acute lung injury and acute respiratory distress syndrome, but the optimal level of applied positive end-expiratory pressure (PEEP) is uncertain. In patients with high pleural pressure on conventional ventilator settings, under-inflation may lead to atelectasis, hypoxemia, and exacerbation of lung injury through "atelectrauma." In such patients, raising PEEP to maintain a positive transpulmonary pressure might improve aeration and oxygenation without causing over-distention. Conversely, in patients with low pleural pressure, maintaining a low PEEP would keep transpulmonary pressure low, avoiding over-distention and consequent "volutrauma." Thus, the currently recommended strategy of setting PEEP without regard to transpulmonary pressure is predicted to benefit some patients while harming others. Recently the use of esophageal manometry to identify the optimal ventilator settings, avoiding both under-inflation and over-inflation, was proposed. This method shows promise but awaits larger clinical trials to assess its impact on clinical outcomes.