Use of a volume- and pressure-limited mechanical ventilation strategy improves clinical outcomes of patients with acute lung injury and acute respiratory distress syndrome (ALI/ARDS). However, the extent to which tidal volumes and inspiratory airway pressures should be reduced to optimize clinical outcomes is a controversial topic. This article addresses the question, “Is there a safe upper limit to inspiratory plateau pressure in patients with ALI/ARDS?” We reviewed data from animal models with and without preexisting lung injury, studies of normal human respiratory system mechanics, and the results of five clinical trials of lung-protective mechanical ventilation strategies. We also present an original analysis of data from the largest of the five clinical trials. The available data from each of these assessments do not support the commonly held view that inspiratory plateau pressures of 30 to 35 cm H2O are safe. We could not identify a safe upper limit for plateau pressures in patients with ALI/ARDS.

Objective: a) Characterize how ventilator and patient variables affect tidal volume during high-frequency oscillatory ventilation; and b) measure tidal volumes in adults with acute respiratory distress syndrome during high-frequency oscillatory ventilation. Design: Observational study. Setting: Research laboratory and medical intensive care unit. Patients: Test lung and patients with acute respiratory distress syndrome. Interventions: Using a previously validated hot wire anemometer placed in series with a Sensormedics 3100B high-frequency ventilator, an endotracheal tube, and a test lung, tidal volume was measured at different combinations of frequency (4, 6, 8, 10, and 12 Hz), pressure amplitude (50, 60, 70, 80, and 90 cm H₂O), mean airway pressure (20, 30, and 40 cm H₂O), test lung compliance (10, 30, and 50 mL/cm H₂O), endotracheal tube internal diameter (6, 7, and 8 mm), bias flow (20, 30, and 40 L/min), and inspiratory/expiratory ratio (1:2 and 1:1). In patients, tidal volume was measured at baseline ventilator settings and at baseline frequency ±2 Hz and baseline pressure amplitude ±10 cm H₂O. Measurements and Main Results: Measured tidal volumes were 23–225 mL during high-frequency oscillatory ventilation of the test lung. A 2-Hz increase in frequency and a 10-cm H₂O increase in pressure amplitude caused a 21.3% ± 4.1% decrease and 21.4% ± 3.4% increase in tidal volume, respectively. Decreasing endotracheal tube internal diameter from 8 mm to 7 mm and from 7 mm to 6 mm caused a 15.3% ± 1.7% and 18.9% ± 2.1% reduction in tidal volume, respectively. Increasing bias flow from 20 L/min to 30 L/min increased tidal volume by 11.2% ± 3.9%. Further increases in bias flow, changes in compliance, and changes in mean airway pressure had little effect. Tidal volumes measured in acute respiratory distress syndrome patients were 44–210 mL. A 2-Hz increase in frequency was associated with a 23.1% ± 6.3% decrease in tidal volume. In contrast to the test lung data, a 10-cm H₂O increase in pressure amplitude resulted in only a 5.6% ± 4.5% increase in tidal volume. Conclusions: Tidal volumes are not uniformly small during high-frequency oscillatory ventilation. The primary determinant of tidal volume in adults with acute respiratory distress syndrome during high-frequency oscillatory ventilation with the Sensormedics 3100B is frequency. Test lung findings suggest that endotracheal tube internal diameter is also an important determinant of tidal volume.

Deep sedation and delirium are common in the ICU. Mechanically ventilated patients with acute lung injury are at especially high risk for deep sedation, delirium, and associated long-term physical and neuropsychiatric impairments. We undertook an ICU-wide structured quality improvement project to decrease sedation and delirium. Prospective quality improvement project in comparison with a retrospective acute lung injury control group. Sixteen-bed medical ICU in an academic teaching hospital with pre-existing use of goal-directed sedation with daily interruption of sedative infusions. Consecutive acute lung injury patients. A "4Es" framework (engage, educate, execute, evaluate) was used as part of the quality improvement process. A new sedation protocol was created and implemented, which recommends a target Richmond Agitation Sedation Scale score of 0 (alert and calm) and requires failure of intermittent sedative dosing prior to starting continuous infusions. In addition, twice-daily delirium screening using the Confusion Assessment Method for the ICU was introduced into routine practice. Sedative use and delirium status in acute lung injury patients after implementation of the quality improvement project (n = 82) were compared with a historical control group (n = 120). During the quality improvement vs. control periods, use of narcotic and benzodiazepine infusions were substantially lower (median proportion of medical ICU days per patient: 33% vs. 74%, and 22% vs. 70%, respectively, both p < 0.001). Further, wakefulness increased (median Richmond Agitation Sedation Scale score per patient: -1.5 vs. -4.0, p < 0.001), and days awake and not delirious increased (median proportion of medical ICU days per patient: 19% vs. 0%, p < 0.001). Through a structured quality improvement process, use of sedative infusions can be substantially decreased and days awake without delirium significantly increased, even in severely ill, mechanically ventilated patients with acute lung injury.

Sepsis accounts for 30% to 50% of all in-hospital deaths in the United States. Other than antibiotics and source control, management strategies are largely supportive with fluid resuscitation and respiratory, renal, and circulatory support. Intravenous vitamin C in conjunction with thiamine and hydrocortisone has recently been suggested to improve outcomes in patients with sepsis in a single-center before-and-after study. However, before this therapeutic strategy is adopted, a rigorous assessment of its efficacy is needed. The Vitamin C, Thiamine and Steroids in Sepsis (VICTAS) trial is a prospective, multi-center, double-blind, adaptive sample size, randomized, placebo-controlled trial. It will enroll patients with sepsis causing respiratory or circulatory compromise or both. Patients will be randomly assigned (1:1) to receive intravenous vitamin C (1.5 g), thiamine (100 mg), and hydrocortisone (50 mg) every 6 h or matching placebos until a total of 16 administrations have been completed or intensive care unit discharge occurs (whichever is first). Patients randomly assigned to the comparator group are permitted to receive open-label stress-dose steroids at the discretion of the treating clinical team. The primary outcome is consecutive days free of ventilator and vasopressor support (VVFDs) in the 30 days following randomization. The key secondary outcome is mortality at 30 days. Sample size will be determined adaptively by using interim analyses with pre-stated stopping rules to allow the early recognition of a large mortality benefit if one exists and to refocus on the more sensitive outcome of VVFDs if an early large mortality benefit is not observed. VICTAS is a large, multi-center, double-blind, adaptive sample size, randomized, placebo-controlled trial that will test the efficacy of vitamin C, thiamine, and hydrocortisone as a combined therapy in patients with respiratory or circulatory dysfunction (or both) resulting from sepsis. Because the components of this therapy are inexpensive and readily available and have very favorable risk profiles, demonstrated efficacy would have immediate implications for the management of sepsis worldwide. ClinicalTrials.gov Identifier: NCT03509350 . First registered on April 26, 2018, and last verified on December 20, 2018. Protocol version: 1.4, January 9, 2019

Cryptococcus neoformans is an encapsulated yeast that causes serious infections in immunocompromised populations. The majority of cases occur in HIV-infected individuals. Disseminated disease is uncommon, and very rarely includes peritonitis.

Background An important, but not well characterized, population receiving intermediate care is that of medical patients admitted directly from the emergency department. Objective To characterize emergency medical patients and their outcomes when admitted to an intermediate care unit with clearly defined admission guidelines. Methods Demographic data, admitting diagnoses, illness severity, comorbid conditions, lengths of stay, and hospital mortality were characterized for all emergency medical patients admitted directly to an intermediate care unit from July through December 2012. Results A total of 317 unique patients were admitted (mean age, 54 [SD, 16] years). Most patients were admitted with respiratory (26.5%) or cardiac (17.0%) syndromes. The mean (SD) Acute Physiology and Chronic Health Evaluation score version II, Simplified Acute Physiology Score version II, and Charlson Comorbidity Index were 15.6 (6.5), 20.7 (11.8), and 2.7 (2.3), respectively. Severity of illness and length of stay were significantly different for patients who required intensive care within 24 hours of admission (n = 16) or later (n = 25), patients who continued with inter mediate care for more than 24 hours (n = 247), and patients who were downgraded or discharged in less than 24 hours (n = 29). Overall hospital mortality was 4.4% (14 deaths). Conclusions Emergency medical patients with moderate severity of illness and comorbidity can be admitted to an intermediate level of care with relatively infrequent transfer to intensive care and relatively low mortality.