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BACKGROUND: Beneficial effects of breathing at FIO2 < 0.21 on disease outcomes have been reported in previous preclinical and clinical studies. However, the safety and intra-hospital feasibility of breathing hypoxic gas for 5 d have not been established. In this study, we examined the physiologic effects of breathing a gas mixture with FIO2 as low as 0.11 in 5 healthy volunteers. METHODS: All 5 subjects completed the study, spending 5 consecutive days in a hypoxic tent, where the ambient oxygen level was lowered in a stepwise manner over 5 d, from FIO2 of 0.16 on the first day to FIO2 of 0.11 on the fifth day of the study. All the subjects returned to an environment at room air on the sixth day. The subjects' SpO2 , heart rate, and breathing frequency were continuously recorded, along with daily blood sampling, neurologic evaluations, transthoracic echocardiography, and mental status assessments. RESULTS: Breathing hypoxia concentration dependently caused profound physiologic changes, including decreased SpO2 and increased heart rate. At FIO2 of 0.14, the mean SpO2 was 92%; at FIO2 of 0.13, the mean SpO2 was 93%; at FIO2 of 0.12, the mean SpO2 was 88%; at FIO2 of 0.11, the mean SpO2 was 85%; and, finally, at an FIO2 of 0.21, the mean SpO2 was 98%. These changes were accompanied by increased erythropoietin levels and reticulocyte counts in blood. All 5 subjects concluded the study with no adverse events. No subjects exhibited signs of mental status changes or pulmonary hypertension. CONCLUSIONS: Results of the current physiologic study suggests that, within a hospital setting, delivering FIO2 as low as 0.11 is feasible and safe in healthy subjects, and provides the foundation for future studies in which therapeutic effects of hypoxia breathing are tested.

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OBJECTIVE: To investigate whether individualized optimization of mechanical ventilation through the implementation of a lung rescue team could reduce the need for venovenous extracorporeal membrane oxygenation in patients with obesity and acute respiratory distress syndrome and decrease ICU and hospital length of stay and mortality. DESIGN: Single-center, retrospective study at the Massachusetts General Hospital from June 2015 to June 2019. PATIENTS: All patients with obesity and acute respiratory distress syndrome who were referred for venovenous extracorporeal membrane oxygenation evaluation due to hypoxemic respiratory failure. INTERVENTION: Evaluation and individualized optimization of mechanical ventilation by the lung rescue team before the decision to proceed with venovenous extracorporeal membrane oxygenation. The control group was those patients managed according to hospital standard of care without lung rescue team evaluation. MEASUREMENT AND MAIN RESULTS: All 20 patients (100%) allocated in the control group received venovenous extracorporeal membrane oxygenation, whereas 10 of 13 patients (77%) evaluated by the lung rescue team did not receive venovenous extracorporeal membrane oxygenation. Patients who underwent lung rescue team evaluation had a shorter duration of mechanical ventilation (p = 0.03) and shorter ICU length of stay (p = 0.03). There were no differences between groups in in-hospital, 30-day, or 1-year mortality. CONCLUSIONS: In this hypothesis-generating study, individualized optimization of mechanical ventilation of patients with acute respiratory distress syndrome and obesity by a lung rescue team was associated with a decrease in the utilization of venovenous extracorporeal membrane oxygenation, duration of mechanical ventilation, and ICU length of stay. Mortality was not modified by the lung rescue team intervention.

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BACKGROUND: Increased pleural pressure affects the mechanics of breathing of people with class III obesity (BMI > 40 kg/m2). RESEARCH QUESTION: What are the acute effects of CPAP titrated to match pleural pressure on cardiopulmonary function in spontaneously breathing patients with class III obesity? STUDY DESIGN AND METHODS: We enrolled six participants with BMI within normal range (control participants, group I) and 12 patients with class III obesity (group II) divided into subgroups: IIa, BMI of 40 to 50 kg/m2; and IIb, BMI of ≥ 50 kg/m2. The study was performed in two phases: in phase 1, participants were supine and breathing spontaneously at atmospheric pressure, and in phase 2, participants were supine and breathing with CPAP titrated to match their end-expiratory esophageal pressure in the absence of CPAP. Respiratory mechanics, esophageal pressure, and hemodynamic data were collected, and right heart function was evaluated by transthoracic echocardiography. RESULTS: The levels of CPAP titrated to match pleural pressure in group I, subgroup IIa, and subgroup IIb were 6 ± 2 cmH2O, 12 ± 3 cmH2O, and 18 ± 4 cmH2O, respectively. In both subgroups IIa and IIb, CPAP titrated to match pleural pressure decreased minute ventilation (IIa, P = .03; IIb, P = .03), improved peripheral oxygen saturation (IIa, P = .04; IIb, P = .02), improved homogeneity of tidal volume distribution between ventral and dorsal lung regions (IIa, P = .22; IIb, P = .03), and decreased work of breathing (IIa, P < .001; IIb, P = .003) with a reduction in both the work spent to initiate inspiratory flow as well as tidal ventilation. In five hypertensive participants with obesity, BP decreased to normal range, without impairment of right heart function. INTERPRETATION: In ambulatory patients with class III obesity, CPAP titrated to match pleural pressure decreased work of breathing and improved respiratory mechanics while maintaining hemodynamic stability, without impairing right heart function. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02523352; URL: www.clinicaltrials.gov.

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Rationale: Obesity is characterized by elevated pleural pressure (Ppl) and worsening atelectasis during mechanical ventilation in patients with acute respiratory distress syndrome (ARDS).Objectives: To determine the effects of a lung recruitment maneuver (LRM) in the presence of elevated Ppl on hemodynamics, left and right ventricular pressure, and pulmonary vascular resistance. We hypothesized that elevated Ppl protects the cardiovascular system against high airway pressure and prevents lung overdistension.Methods: First, an interventional crossover trial in adult subjects with ARDS and a body mass index ≥ 35 kg/m2 (n = 21) was performed to explore the hemodynamic consequences of the LRM. Second, cardiovascular function was studied during low and high positive end-expiratory pressure (PEEP) in a model of swine with ARDS and high Ppl (n = 9) versus healthy swine with normal Ppl (n = 6).Measurements and Main Results: Subjects with ARDS and obesity (body mass index = 57 ± 12 kg/m2) after LRM required an increase in PEEP of 8 (95% confidence interval [95% CI], 7-10) cm H2O above traditional ARDS Network settings to improve lung function, oxygenation and [Formula: see text]/[Formula: see text] matching, without impairment of hemodynamics or right heart function. ARDS swine with high Ppl demonstrated unchanged transmural left ventricular pressure and systemic blood pressure after the LRM protocol. Pulmonary arterial hypertension decreased (8 [95% CI, 13-4] mm Hg), as did vascular resistance (1.5 [95% CI, 2.2-0.9] Wood units) and transmural right ventricular pressure (10 [95% CI, 15-6] mm Hg) during exhalation. LRM and PEEP decreased pulmonary vascular resistance and normalized the [Formula: see text]/[Formula: see text] ratio.Conclusions: High airway pressure is required to recruit lung atelectasis in patients with ARDS and class III obesity but causes minimal overdistension. In addition, patients with ARDS and class III obesity hemodynamically tolerate LRM with high airway pressure.Clinical trial registered with www.clinicaltrials.gov (NCT02503241).

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OBJECTIVES: The impact of tidal volume on outcomes in mechanically ventilated children with pediatric acute respiratory distress syndrome remains unclear. To date, observational investigations have failed to calculate tidal volume based on standardized corrections of weight. We investigated the impact of tidal volume on mortality and probability of extubation in pediatric acute respiratory distress syndrome using ideal body weight-adjusted tidal volume. DESIGN: Retrospective analysis of an ongoing prospective cohort of pediatric acute respiratory distress syndrome patients. Tidal volume was calculated based on actual body weight and two different formulations of ideal body weight. SETTING: PICU at a large, tertiary care children's hospital. PATIENTS: Pediatric acute respiratory distress syndrome patients on conventional ventilation with a documented height or length. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 483 patients with a measured height or length at pediatric acute respiratory distress syndrome onset included in the final analysis, with 73 nonsurvivors (15%). At 24 hours, there remained 400 patients on conventional ventilation. When calculating tidal volume based on ideal body weight by either method, volumes were larger both at onset and at 24 hours compared with tidal volume based on actual body weight (all p < 0.001), and the proportion of patients being ventilated with tidal volumes greater than 10 mL/kg based on ideal body weight was larger both at onset (12.4% and 15.5%) and 24 hours (10.3% and 11.5%) compared with actual body weight at onset (3.5%) and 24 hours (4.0%) (all p < 0.001). Tidal volume, based on both actual body weight and ideal body weight, was not associated with either increased mortality or decreased probability of extubation after adjusting for oxygenation index in the whole cohort, whereas associations between higher tidal volume and poor outcomes were seen in subgroup analyses in overweight children and in severe pediatric acute respiratory distress syndrome. CONCLUSIONS: Our retrospective analysis of a cohort of pediatric acute respiratory distress syndrome patients did not find a consistent association between tidal volume adjusted for ideal body weight and outcomes, although an association may exist in certain subgroups. Although it remains to be shown in a prospective trial whether high volumes or pressures are injurious in pediatric acute respiratory distress syndrome, tidal volume is likely an imprecise parameter for titrating lung-protective ventilation.

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BACKGROUND: Biofilm on the surface of endotracheal tubes (ETTs) is associated with ventilator-associated pneumonia. The use of silver-coated ETTs has been suggested to reduce the occurrence of ventilator-associated pneumonia by preventing biofilm formation. However, mucus accumulation can reduce the antibacterial activity of silver-coated ETTs by isolating bacterial colonies from the silver surface. We hypothesized that, in mechanically ventilated subjects, periodic removal of secretions through the use of a cleaning device would enhance the antimicrobial properties of silver-coated ETTs and thus reduce bacterial colonization. METHODS: Subjects were randomized to either standard suctioning (blind tracheal suctioning, control group) or blind tracheal suctioning plus cleaning maneuver every 8 h (treatment group). Tracheal aspirates were collected immediately before extubation for microbiological culture. After extubation, ETTs were collected for both cultural and non-cultural microbiological analysis and biofilm isolation. RESULTS: 39 subjects expected to be ventilated for > 48 h were enrolled; 36 ETTs (18 control, 18 treatment) and 29 tracheal samples (15 control, 14 treatment) were collected. Among the ETTs positive for bacterial colonization (15 vs 9, P = .18), cleaning maneuvers did not reduce microbial load, shown as the decimal logarithm of colony-forming units (CFU) per mL (1.6 ± 1.2 vs 0.9 ± 1.2 logCFU/mL, P = .15). There was a trend toward decreased biofilm deposition (439.5 ± 29.0 vs 288.9 ± 157.7 mg, P = .09) in the treated ETTs. No significant differences were observed in the number of positive tracheal aspirates (13 vs 10, P = .39) or in the microbial load (4.8 ± 4.0 vs 4.2 ± 3.8 logCFU/mL, P = .70) of tracheal secretions. Finally, no differences in the microbial load of Gram-positive organisms, Gram-negative organisms, or yeasts were found between the ETTs and tracheal aspirates of the 2 groups. CONCLUSIONS: In 39 critically-ill subjects intubated with silver-coated ETTs, periodic cleaning maneuvers did not decrease bacterial colonization of the ETTs and did not lower respiratory tract colonization compared to the standard suctioning. (Clinicaltrials.gov registration NCT02120001.).

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Morbidly obese, critically ill patients are prone to develop hypoxemic respiratory failure and ventilator dependency. The best method for recruiting the lungs of these patients and keeping alveoli open without causing injury remains unclear. We present the case of a 31-year-old patient with severe refractory hypoxemia reversed by lung recruitment maneuvers and subsequent application of positive end-expiratory pressure (PEEP) at a level determined by a decremental PEEP trial. The patient was extubated at a high PEEP level of 22 cm H2O followed by noninvasive ventilatory support after extubation. This case suggests that a recruitment maneuver followed by PEEP titration is necessary in obese patients for optimizing mechanical ventilation. Extubation to noninvasive ventilatory support with the identified optimal PEEP may decrease an inappropriate increased work of breathing and the risk of reintubation.

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With a rising incidence of obesity in the United States, anesthesiologists are faced with a larger volume of obese patients coming to the operating room as well as obese patients with ever-larger body mass indices (BMIs). While there are many cardiovascular and endocrine issues that clinicians must take into account when caring for the obese patient, one of the most prominent concerns of the anesthesiologist in the perioperative setting should be the status of the lung. Because the pathophysiology of reduced lung volumes in the obese patient differs from that of the ARDS patient, the best approach to keeping the obese patient's lung open and adequately ventilated during mechanical ventilation is unique. Although strong evidence and research are lacking regarding how to best ventilate the obese surgical patient, we aim with this review to provide an assessment of the small amount of research that has been conducted and the pathophysiology we believe influences the apparent results. We will provide a basic overview of the anatomy and pathophysiology of the obese respiratory system and review studies concerning pre-, intra-, and postoperative respiratory care. Our focus in this review centers on the best approach to keeping the lung recruited through the prevention of compression atelectasis and the maintaining of physiological lung volumes. We recommend the use of PEEP via noninvasive ventilation (NIV) before induction and endotracheal intubation, the use of both PEEP and periodic recruitment maneuvers during mechanical ventilation, and the use of PEEP via NIV after extubation. It is our hope that by studying the underlying mechanisms that make ventilating obese patients so difficult, future research can be better tailored to address this increasingly important challenge to the field of anesthesia.

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OBJECTIVE: The approach to applying positive end-expiratory pressure in morbidly obese patients is not well defined. These patients frequently require prolonged mechanical ventilation, increasing the risk for failed liberation from ventilatory support. We hypothesized that lung recruitment maneuvers and titration of positive end-expiratory pressure were both necessary to improve lung volumes and the elastic properties of the lungs, leading to improved gas exchange. DESIGN: Prospective, crossover, nonrandomized interventional study. SETTING: Medical and surgical ICUs at Massachusetts General Hospital. PATIENTS: Critically ill, mechanically ventilated morbidly obese (body mass index > 35 kg/m(2)) patients (n = 14). INTERVENTIONS: This study evaluated two methods of titrating positive end-expiratory pressure; both trials were done utilizing positive end-expiratory pressure titration and recruitment maneuvers while measuring hemodynamics and respiratory mechanics. Measurements were obtained at the baseline positive end-expiratory pressure set by the clinicians, at zero positive end-expiratory pressure, at best positive end-expiratory pressure identified through esophageal pressure measurement before and after a recruitment maneuver, and at best positive end-expiratory pressure identified through a best decremental positive end-expiratory pressure trial. MEASUREMENTS AND MAIN RESULTS: The average body mass index was 50.7 ± 16.0 kg/m(2). The two methods of evaluating positive end-expiratory pressure identified similar optimal positive end-expiratory pressure levels (20.7 ± 4.0 vs 21.3 ± 3.8 cm H2O; p = 0.40). End-expiratory pressure titration increased end-expiratory lung volumes (Δ11 ± 7 mL/kg; p < 0.01) and oxygenation (Δ86 ± 50 torr; p < 0.01) and decreased lung elastance (Δ5 ± 5 cm H2O/L; p < 0.01). Recruitment maneuvers followed by titrated positive end-expiratory pressure were effective at increasing end-expiratory lung volumes while decreasing end-inspiratory transpulmonary pressure, suggesting an improved distribution of lung aeration and reduction of overdistension. The positive end-expiratory pressure levels set by the clinicians (11.6 ± 2.9 cm H2O) were associated with lower lung volumes, worse elastic properties of the lung, and lower oxygenation. CONCLUSIONS: Commonly used positive end-expiratory pressure by clinicians is inadequate for optimal mechanical ventilation of morbidly obese patients. A recruitment maneuver followed by end-expiratory pressure titration was found to significantly improve lung volumes, respiratory system elastance, and oxygenation.

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