Person:

Loring, Stephen

Introduction: Optimal ventilator management for patients with acute respiratory distress syndrome (ARDS) remains uncertain. Lower tidal volume ventilation appears to be beneficial, but optimal management of positive end-expiratory pressure (PEEP) remains unclear. The Esophageal Pressure-Guided Ventilation 2 Trial (EPVent2) aims to examine the impact of mechanical ventilation directed at maintaining a positive transpulmonary pressure (PTP) in patients with moderate-to-severe ARDS. Methods and analysis EPVent2 is a multicentre, prospective, randomised, phase II clinical trial testing the hypothesis that the use of a PTP-guided ventilation strategy will lead to improvement in composite outcomes of mortality and time off the ventilator at 28 days as compared with a high-PEEP control. This study will enrol 200 study participants from 11 hospitals across North America. The trial will utilise a primary composite end point that incorporates death and days off the ventilator at 28 days to test the primary hypothesis that adjusting ventilator pressure to achieve positive PTP values will result in improved mortality and ventilator-free days. Ethics and dissemination Safety oversight will be under the direction of an independent Data and Safety Monitoring Board (DSMB). Approval of the protocol was obtained from the DSMB prior to enrolling the first study participant. Approvals of the protocol as well as informed consent documents were also obtained from the Institutional Review Board of each participating institution prior to enrolling study participants at each respective site. The findings of this investigation, as well as associated ancillary studies, will be disseminated in the form of oral and abstract presentations at major national and international medical specialty meetings. The primary objective and other significant findings will also be presented in manuscript form. All final, published manuscripts resulting from this protocol will be submitted to PubMed Central in accordance with the National Institute of Health Public Access Policy. Trial registration number ClinicalTrials.gov under number NCT01681225.

Esophageal pressure can be used to approximate pleural pressure and might be clinically useful, particularly in the obese e.g to guide mechanical ventilator settings in critical illness. However, mediastinal artifact (the difference between true pleural pressure and esophageal pressure) may limit acceptance of the measurement, and reproducibility of esophageal pressure measurements remains unknown. Therefore, we aimed to assess the effect of body posture on esophageal pressure in a cohort of obese but healthy subjects, some of whom had multiple measurements, to address the clinical robustness of esophageal manometry. Twenty-five overweight and obese subjects (BMI>25kg/m2) and 11 control lean subjects (BMI<25kg/m2) underwent esophageal manometry with pressures measured seated and supine. Twenty overweight and obese subjects had measurements repeated after ~1-2 weeks. Anthropometric data and sitting and supine spirometry were recorded. The average end-expiratory esophageal pressures sitting and supine were greater in the overweight and obese group than the lean group (sitting −0.1±2.1 vs. −3.3±1.2cmH2O, supine 9.3±3.3 vs. 6.9±2.8cmH2O, respectively). The mean differences between repeated measurements were small (−0.3 ± 1.7cmH2O sitting and −0.1 ± 1.5cmH2O supine). Esophageal pressures correlated with a number of anthropometric and spirometric variables. In conclusion, esophageal pressures are slightly greater in overweight and obese subjects than lean subjects; but changes with position are similar in both groups. These data indicate that mediastinal weight and postural effects on esophageal pressure are within a clinically acceptable range, and suggest that esophageal manometry can be used to inform clinical decision making across wide range of body types.

A 33-year-old woman underwent a right-sided pneumonectomy in 1995 for treatment of a lung adenocarcinoma. As expected, there was an abrupt decrease in her vital capacity, but unexpectedly, it increased during the subsequent 15 years. Serial computed tomographic (CT) scans showed progressive enlargement of the remaining left lung and an increase in tissue density. Magnetic resonance imaging (MRI) with the use of hyperpolarized helium-3 gas showed overall acinar-airway dimensions that were consistent with an increase in the alveolar number rather than the enlargement of existing alveoli, but the alveoli in the growing lung were shallower than in normal lungs. This study provides evidence that new lung growth can occur in an adult human.

Abstract The critical care management of pleural air leaks can be challenging in all patients, but particularly in patients on mechanical ventilation. To investigate the effect of central airway pressure and pleural pressure on pulmonary air leaks, we studied orotracheally intubated mice with pleural injuries. We used clinically relevant variables – namely, airway pressure and pleural pressure – to investigate flow through peripheral air leaks. The model studied the pleural injuries using a pressure‐decay maneuver. The pressure‐decay maneuver involved a 3 sec ramp to 30 cmH20 followed by a 3 sec breath hold. After pleural injury, the pressure‐decay maneuver demonstrated a distinctive airway pressure time history. Peak inflation was followed by a rapid decrease to a lower plateau phase. The decay phase of the inflation maneuver was influenced by the injury area. The rate of pressure decline with multiple injuries (28 ± 8 cmH20/sec) was significantly greater than a single injury (12 ± 3 cmH2O/sec) (P < 0.05). In contrast, the plateau phase pressure was independent of injury surface area, but dependent upon transpulmonary pressure. The mean plateau transpulmonary pressure was 18 ± 0.7 cm H2O. Finally, analysis of the inflation ramp demonstrated that nearly all volume loss occurred at the end of inflation (P < 0.001). We conclude that the air flow through peripheral lung injuries was greatest at increased lung volumes and limited by peripheral airway closure. In addition to suggesting an intrinsic mechanism for limiting flow through peripheral air leaks, these findings suggest the utility of positive end‐expiratory pressure and negative pleural pressure to maintain lung volumes in patients with pleural injuries.