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...

Intensive renal support in critically ill patients with acute kidney injury did not decrease mortality, improve recovery of kidney function, or reduce the rate of nonrenal organ failure as compared with less-intensive therapy involving a defined dose of intermittent hemodialysis three times per week and continuous renal-replacement therapy at 20 ml per kilogram per hour. (ClinicalTrials.gov number, NCT00076219.)

Lactic acidosis is frequently encountered in the intensive care unit. It occurs when there is an imbalance between production and clearance of lactate. Although lactic acidosis is often associated with a high anion gap and is generally defined as a lactate level >5 mmol/L and a serum pH <7.35, the presence of hypoalbuminemia may mask the anion gap and concomitant alkalosis may raise the pH. The causes of lactic acidosis are traditionally divided into impaired tissue oxygenation (Type A) and disorders in which tissue oxygenation is maintained (Type B). Lactate level is often used as a prognostic indicator and may be predictive of a favorable outcome if it normalizes within 48 hours. The routine measurement of serum lactate, however, should not determine therapeutic interventions. Unfortunately, treatment options remain limited and should be aimed at discontinuation of any offending drugs, treatment of the underlying pathology, and maintenance of organ perfusion. The mainstay of therapy of lactic acidosis remains prevention.

The mortality rate for patients with acute renal failure (ARF) remains unacceptably high. Although dialysis removes waste products and corrects fluid imbalance, it does not perform the absorptive, metabolic, endocrine, and immunologic functions of normal renal tubule cells. The renal tubule assist device (RAD) is composed of a conventional hemofilter lined by monolayers of renal cells. For testing whether short-term (up to 72 h) treatment with the RAD would improve survival in patients with ARF compared with conventional continuous renal replacement therapy (CRRT), a Phase II, multicenter, randomized, controlled, open-label trial involving 58 patients who had ARF and required CRRT was performed. Forty patients received continuous venovenous hemofiltration ϩ RAD, and 18 received CRRT alone. The primary efficacy end point was all-cause mortality at 28 d; additional end points included all-cause mortality at 90 and 180 d, time to recovery of renal function, time to intensive care unit and hospital discharge, and safety. At day 28, the mortality rate was 33% in the RAD group and 61% in the CRRT group. Kaplan-Meier analysis revealed that survival through day 180 was significantly improved in the RAD group, and Cox proportional hazards models suggested that the risk for death was approximately 50% of that observed in the CRRT-alone group. RAD therapy was also associated with more rapid recovery of kidney function, was well tolerated, and had the expected adverse event profile for critically ill patients with ARF. Acute renal failure (ARF) arising from acute kidney injury (AKI) and acute tubular necrosis (ATN) secondary to nephrotoxic and/or ischemic renal tubule cell injury commonly results in a cascade of events culminating in multiorgan failure and death. Mortality rates from AKI requiring renal replacement therapy range from 50 to 70%. 1,2 This high mortality rate has persisted over the past several decades despite greater understanding of the pathophysiology of the disorder and improvements in hemodialysis and hemofiltration therapy.The pathophysiology of this disease is initiated with injury to the cellular elements of the kidney,

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