BACKGROUNDVasodilatory shock that does not respond to high-dose vasopressors is associated with high mortality. We investigated the effectiveness of angiotensin II for the treatment of patients with this condition. METHODSWe randomly assigned patients with vasodilatory shock who were receiving more than 0.2 μg of norepinephrine per kilogram of body weight per minute or the equivalent dose of another vasopressor to receive infusions of either angiotensin II or placebo. The primary end point was a response with respect to mean arterial pressure at hour 3 after the start of infusion, with response defined as an increase from baseline of at least 10 mm Hg or an increase to at least 75 mm Hg, without an increase in the dose of background vasopressors. RESULTSA total of 344 patients were assigned to one of the two regimens; 321 received a study intervention (163 received angiotensin II, and 158 received placebo) and were included in the analysis. The primary end point was reached by more patients in the angiotensin II group (114 of 163 patients, 69.9%) than in the placebo group (37 of 158 patients, 23.4%) (odds ratio, 7.95; 95% confidence interval [CI], 4.76 to 13.3; P<0.001). At 48 hours, the mean improvement in the cardiovascular Sequential Organ Failure Assessment (SOFA) score (scores range from 0 to 4, with higher scores indicating more severe dysfunction) was greater in the angiotensin II group than in the placebo group (−1.75 vs. −1.28, P = 0.01). Serious adverse events were reported in 60.7% of the patients in the angiotensin II group and in 67.1% in the placebo group. Death by day 28 occurred in 75 of 163 patients (46%) in the angiotensin II group and in 85 of 158 patients (54%) in the placebo group (hazard ratio, 0.78; 95% CI, 0.57 to 1.07; P = 0.12). CONCLUSIONS 420T h e ne w e ngl a nd jou r na l o f m e dicine S hock is a life-threatening syndrome characterized by decreased organ perfusion that can progress to irreversible organ failure. 1 Vasodilatory shock is the most common type of shock and is characterized by peripheral vasodilation and reduced blood pressure despite preserved cardiac output. 2 Vasodilatory shock requires immediate treatment to ensure organ perfusion through the reestablishment of adequate blood pressure while the underlying cause of shock is identified and treated. 3 Vasopressors are used when intravenous fluid resuscitation alone fails to restore blood pressure. Patients with severe vasodilation who have hypotension despite the use of high doses of vasopressors have a poor prognosis, with 30-day all-cause mortality exceeding 50%. 4,5 Currently, only two classes of vasopressors are available: catecholamines (and other sympathomimetic amines) and vasopressin. 3 Both classes have narrow therapeutic windows owing to substantial toxic effects at high doses. 6 However, when hypotension occurs, human physiology engages a third system, which is represented by hormones in the renin-angiotensin-aldosterone system (RAAS). 7 Previously, modified bovine angiotensin II was shown to elicit consis...

Our study supports the feasibility of a conservative oxygenation strategy in patients receiving IMV. Larger randomized controlled trials of this intervention appear justified. Clinical trial registered with Australian New Zealand Clinical Trials Registry (ACTRN 12613000505707).

Background: Patients who are going thorugh mechanical ventilation in the intensive care unit (ICU) often receive a high fraction of inspired oxygen (Fio2 ) and have a high arterial oxygen tension. The conservative use of oxygen may reduce oxygen exposure, diminish lung and systemic oxidative injury, and thereby increase the number of ventilator-free days (days alive and free from mechanical ventilation). Methods: We randomly assigned 1000 adult patients who were anticipated to require mechanical ventilation beyond the day after recruitment in the ICU to receive conservative or usual oxygen therapy. In the two groups, the default lower limit for oxygen saturation as measured by pulse oximetry (Spo2 ) was 90%. In the conservativeoxygen group, the upper limit of the Spo2 alarm was set to sound when the level reached 97%, and the Fio2 was decreased to 0.21 if the Spo2 was above the acceptable lower limit. In the usual-oxygen group, there were no specific measures limiting the Fio2 or the Spo2 . The primary outcome was the number of ventilatorfree days from randomization until day 28. Results: The number of ventilator-free days did not differ significantly between the conservative-oxygen group and the usualoxygen group, with a median duration of 21.3 days (interquartile range, 0 to 26.3) and 22.1 days (interquartile range, 0 to 26.2), respectively, for an absolute difference of −0.3 days (95% confidence interval [CI], −2.1 to 1.6; P=0.80). The conservativeoxygen group spent more time in the ICU with an Fio2 of 0.21 than the usual-oxygen group, with a median duration of 29 hours (interquartile range, 5 to 78) and 1 hour (interquartile range, 0 to 17), respectively (absolute difference, 28 hours; 95% CI, 22 to 34); the conservative-oxygen group spent less time with an Spo2 exceeding 96%, with a duration of 27 hours (interquartile range, 11 to 63.5) and 49 hours (interquartile range, 22 to 112), respectively (absolute difference, 22 hours; 95% CI, 14 to 30). At 180 days, mortality was 35.7% in the conservative-oxygen group and 34.5% in the usual-oxygen group, for an unadjusted odds ratio of 1.05 (95% CI, 0.81 to 1.37). Conclusions: In adults undergoing mechanical ventilation in the ICU, the use of conservative oxygen therapy, as compared with usual oxygen therapy, did not significantly affect the number of ventilator-free days.

Rationale: A novel model of phenotypes based on set thresholds of respiratory system compliance (Crs) was recently postulated in context of coronavirus disease (COVID-19) acute respiratory distress syndrome (ARDS). In particular, the dissociation between the degree of hypoxemia and Crs was characterized as a distinct ARDS phenotype. Objectives: To determine whether such Crs-based phenotypes existed among patients with ARDS before the COVID-19 pandemic and to closely examine the Crs–mortality relationship. Methods: We undertook a secondary analysis of patients with ARDS, who were invasively ventilated on controlled modes and enrolled in a large, multinational, epidemiological study. We assessed Crs, degree of hypoxemia, and associated Crs-based phenotypic patterns with their characteristics and outcomes. Measurements and Main Results: Among 1,117 patients with ARDS who met inclusion criteria, the median Crs was 30 (interquartile range, 23–40) ml/cm H 2 O. One hundred thirty-six (12%) patients had preserved Crs (≥50 ml/cm H 2 O; phenotype with low elastance [“phenotype L”]), and 827 (74%) patients had poor Crs (<40 ml/cm H 2 O; phenotype with high elastance [“phenotype H”]). Compared with those with phenotype L, patients with phenotype H were sicker and had more comorbidities and higher hospital mortality (32% vs. 45%; P < 0.05). A near complete dissociation between Pa O 2 /F i O 2 and Crs was observed. Of 136 patients with phenotype L, 58 (43%) had a Pa O 2 /F i O 2 < 150. In a multivariable-adjusted analysis, the Crs was independently associated with hospital mortality (adjusted odds ratio per ml/cm H 2 O increase, 0.988; 95% confidence interval, 0.979–0.996; P = 0.005). Conclusions: A wide range of Crs was observed in non–COVID-19 ARDS. Approximately one in eight patients had preserved Crs. Pa O 2 /F i O 2 and Crs were dissociated. Lower Crs was independently associated with higher mortality. The Crs–mortality relationship lacked a clear transition threshold.