BACKGROUND Survival of patients with acute lung injury or the acute respiratory distress syndrome (ARDS) has been improved by ventilation with small tidal volumes and the use of positive end-expiratory pressure (PEEP); however, the optimal level of PEEP has been difficult to determine. In this pilot study, we estimated transpulmonary pressure with the use of esophageal balloon catheters. We reasoned that the use of pleural-pressure measurements, despite the technical limitations to the accuracy of such measurements, would enable us to find a PEEP value that could maintain oxygenation while preventing lung injury due to repeated alveolar collapse or overdistention. METHODS We randomly assigned patients with acute lung injury or ARDS to undergo mechanical ventilation with PEEP adjusted according to measurements of esophageal pressure (the esophageal-pressure–guided group) or according to the Acute Respiratory Distress Syndrome Network standard-of-care recommendations (the control group). The primary end point was improvement in oxygenation. The secondary end points included respiratory-system compliance and patient outcomes. RESULTS The study reached its stopping criterion and was terminated after 61 patients had been enrolled. The ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen at 72 hours was 88 mm Hg higher in the esophageal-pressure–guided group than in the control group (95% confidence interval, 78.1 to 98.3; P = 0.002). This effect was persistent over the entire follow-up time (at 24, 48, and 72 hours; P = 0.001 by repeated-measures analysis of variance). Respiratory-system compliance was also significantly better at 24, 48, and 72 hours in the esophageal-pressure–guided group (P = 0.01 by repeated-measures analysis of variance). CONCLUSIONS As compared with the current standard of care, a ventilator strategy using esophageal pressures to estimate the transpulmonary pressure significantly improves oxygenation and compliance. Multicenter clinical trials are needed to determine whether this approach should be widely adopted. (ClinicalTrials.gov number, NCT00127491.)

Importance: Adjusting positive end-expiratory pressure (PEEP) to offset pleural pressure might attenuate lung injury and improve patient outcomes in acute respiratory distress syndrome (ARDS). Objective: To determine whether PEEP titration guided by esophageal pressure (PES), an estimate of pleural pressure, was more effective than empiric high PEEP-FiO2 in moderate-to-severe ARDS. Design, Setting, and Participants: Phase-II randomized clinical trial conducted at 14 hospitals in North America. Two hundred mechanically ventilated patients aged ≥ 16 years with moderate-to-severe ARDS (PaO2:FiO2 ≤ 200) were enrolled between October 31, 2012 and September 14, 2017; long-term follow-up completed July 30, 2018. Interventions: Participants were randomized to PES-guided PEEP (n = 102) or empiric high PEEP-FiO2 (n = 98). All participants received low tidal volumes. Main Outcomes and Measures: The primary outcome was a ranked composite score incorporating death and days free from mechanical ventilation among survivors through day 28. Pre-specified secondary outcomes included 28-day mortality, days free from mechanical ventilation among survivors, and need for rescue therapy. Results: Two hundred patients were enrolled (mean [SD] age 56 [16] years; 46% female) and completed 28-day follow-up. The primary composite endpoint was not significantly different between treatment groups (probability of more favorable outcome with PES-guided PEEP: 49.6% [95% CI 41.7% to 57.5%]; p = 0.92). At 28 days, 33 of 102 patients (32.4%) assigned to PES-guided PEEP and 33 of 98 patients (30.6%) assigned to empiric PEEP-FiO2 died (risk difference 1.7% [95% CI −11.1% to 14.6%]; p = 0.88). Days free from mechanical among survivors was not significantly different (22 [15-24] vs. 21 [16.5-24] days; median difference 0 [95% CI −1 to 2] days; p = 0.85). Patients assigned to PES-guided PEEP were significantly less likely to receive rescue therapy (4/102 [3.9%] vs. 12/98 [12.2%]; risk difference −8.3% [95% CI −15.8% to −0.8%]; p = 0.04). None of the seven other pre-specified secondary clinical endpoints were significantly different. Adverse events included gross barotrauma, which occurred in six patients with PES-guided PEEP and five patients with empiric PEEP-FiO2. Conclusions and Relevance: Among patients with moderate-to-severe ARDS, PES-guided PEEP, compared to empiric high PEEP-FiO2, resulted in no significant difference in death and days free from mechanical ventilation. These findings do not support PES-guided PEEP titration in ARDS. Trial Registration: ClinicalTrials.gov identifier

In patients in acute respiratory failure, elevated esophageal pressures suggest that chest wall mechanical properties often contribute substantially and unpredictably to total respiratory impedance, and therefore Pao may not adequately predict PL or lung distention. Systematic use of esophageal manometry has the potential to improve ventilator management in acute respiratory failure by providing more direct assessment of lung distending pressure.

Septic cardiomyopathy is an important contributor to organ dysfunction in sepsis. Guided treatment of septic cardiomyopathy may affect patients' prognosis, especially when their cardiac index is substantially decreased. The implication of septic cardiomyopathy for both short- and long-term outcomes is an important area for future investigation.

Acute lung injury can be worsened by inappropriate mechanical ventilation, and numerous experimental studies suggest that ventilator-induced lung injury is increased by excessive lung inflation at end inspiration or inadequate lung inflation at end expiration. Lung inflation depends not only on airway pressures from the ventilator but, also, pleural pressure within the chest wall. Although esophageal pressure (Pes) measurements are often used to estimate pleural pressures in healthy subjects and patients, they are widely mistrusted and rarely used in critical illness. To assess the credibility of Pes as an estimate of pleural pressure in critically ill patients, we compared Pes measurements in 48 patients with acute lung injury with simultaneously measured gastric and bladder pressures (Pga and P(blad)). End-expiratory Pes, Pga, and P(blad) were high and varied widely among patients, averaging 18.6 +/- 4.7, 18.4 +/- 5.6, and 19.3 +/- 7.8 cmH(2)O, respectively (mean +/- SD). End-expiratory Pes was correlated with Pga (P = 0.0004) and P(blad) (P = 0.0104) and unrelated to chest wall compliance. Pes-Pga differences were consistent with expected gravitational pressure gradients and transdiaphragmatic pressures. Transpulmonary pressure (airway pressure - Pes) was -2.8 +/- 4.9 cmH(2)O at end exhalation and 8.3 +/- 6.2 cmH(2)O at end inflation, values consistent with effects of mediastinal weight, gravitational gradients in pleural pressure, and airway closure at end exhalation. Lung parenchymal stress measured directly as end-inspiratory transpulmonary pressure was much less than stress inferred from the plateau airway pressures and lung and chest wall compliances. We suggest that Pes can be used to estimate transpulmonary pressures that are consistent with known physiology and can provide meaningful information, otherwise unavailable, in critically ill patients.

Orthotopic liver transplantation (OLT) is one of the most demanding surgical procedures performed. Intraoperative bleeding can be substantial and related to both surgical and nonsurgical causes. A less common but previously reported phenomenon is intraoperative cardiopulmonary thromboembolism precipitating major patient morbidity and mortality. In this paper, we present four cases of intraoperative thromboembolism during OLT. These cases were performed without the concomitant use of antifibrinolytic drugs. We performed a review and analysis of previously reported cases of intraoperative thromboembolism during OLT. Possible causes of thromboembolism, clinical management, use of thromboelastography, and the role of antifibrinolytic drugs are discussed.

Consent to participate: Written informed consent was obtained from all subjects or their legally authorised representatives. Consent for publication: Not applicableAvailability of data and material: De-identified data collected during the trial will be made available upon reasonable request to researchers who provide a methodologically sound proposal, after approval by the study authors, and with a signed data access agreement. Questions about data are handled by the corresponding author.

AGPs = aerosol-generating procedures; BiPAP = bilevel positive airway pressure; CDC = Centers for Disease Control and Prevention; COVID-19 = coronavirus disease 2019; CPAP = continuous positive airway pressure; ETT = endotracheal tube; Fio 2 = fraction of inspired oxygen; HCWs = health care workers; HEPA = high-efficiency particulate air; ICU = intensive care unit; INR = international normalized ratio; MERS = Middle East Respiratory Syndrome; OR = operating room; Pao 2 = partial pressure of oxygen; PAPRs = powered air-purifying respirators; PCR = polymerase chain reaction; PEEP = positive end-expiratory pressure; PPE = personal protective equipment; SARS = severe acute respiratory syndrome; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; VTE = venous thromboembolism; WHO = World Health Organization C oronavirus infections in humans can vary from mild diseases, such as the common cold, to severe end-organ dysfunction such as acute respiratory distress syndrome. 1 The morbidity, mortality, and blistering pace of transmission, of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)The morbidity, mortality, and blistering pace of transmission of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to an unprecedented worldwide health crisis. Coronavirus disease 2019 (COVID-19), the disease produced by SARS-CoV-2 infection, is remarkable for persistent, severe respiratory failure requiring mechanical ventilation that places considerable strain on critical care resources. Because recovery from COVID-19-associated respiratory failure can be prolonged, tracheostomy may facilitate patient management and optimize the use of mechanical ventilators. Several important considerations apply to plan tracheostomies for COVID-19-infected patients. After performing a literature review of tracheostomies during the severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS) outbreaks, we synthesized important learning points from these experiences and suggested an approach for perioperative teams involved in these procedures during the COVID-19 pandemic. Multidisciplinary teams should be involved in decisions regarding timing and appropriateness of the procedure. As the theoretical risk of disease transmission is increased during aerosol-generating procedures (AGPs), stringent infectious precautions are warranted. Personal protective equipment (PPE) should be available and worn by all personnel present during tracheostomy. The number of people in the room should be limited to those absolutely necessary. Using the most experienced available operators will minimize the total time that staff is exposed to an infectious aerosolized environment. An approach that secures the airway in the safest and quickest manner will minimize the time any part of the airway is open to the environment. Deep neuromuscular blockade (train-of-four ratio = 0) will facilitate surgical exposure and prevent aerosolization due to patient movement or coughing. For percutaneous tracheost...