Angiotensin II in Refractory Septic Shock

Antonucci, Elio; Gleeson, Patrick; Annoni, Filippo; Agosta, Sara; Orlando, Sergio; Taccone, Fabio Silvio; Velissaris, Dimitrios; Scolletta, Sabino

doi:10.1097/shk.0000000000000807

“…7 Previously, modified bovine angiotensin II was shown to elicit consistent vasopressor effects in patients with shock. [8][9][10] In a recent pilot study, addition of human angiotensin II to catecholamine and vasopressin therapy increased mean arterial pressure in patients with vasodilatory shock, allowing reductions in the dose of catecholamines. 11 These findings prompted the initiation of the phase 3 Angiotensin II for the Treatment of High-Output Shock (ATHOS-3) trial to determine whether the addition of angiotensin II to background vasopressors would improve blood pressure in patients with catecholamine-resistant vasodilatory shock.…”

mentioning

confidence: 99%

Angiotensin II for the Treatment of Vasodilatory Shock

Khanna

¹

,

English

²

,

Wang

³

et al. 2017

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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...

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“…Several studies have investigated the effects of alternative vasopressors for treatment of vasodilatory shock 4 5. Angiotensin II was suggested as potential catecholamine-sparing agent for the treatment of refractory vasodilatory shock6.…”

Section: Contextmentioning

confidence: 99%

“…The renin-angiotensin-aldosterone system is a key determinant of shock response, together with endogenous catecholamines and vasopressin6. Although current data are insufficient to recommend widespread use of angiotensin II, it may become a fundamental therapeutic intervention in the future.…”

Section: Implications For Practicementioning

confidence: 99%

Angiotensin II increases blood pressure in patients with refractory vasodilatory shock

Landoni

¹

,

Belletti²

2018

BMJ EBM

0

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“…7 Previously, modified bovine angiotensin II was shown to elicit consistent vasopressor effects in patients with shock. [8][9][10] In a recent pilot study, addition of human angiotensin II to catecholamine and vasopressin therapy increased mean arterial pressure in patients with vasodilatory shock, allowing reductions in the dose of catecholamines. 11 These findings prompted the initiation of the phase 3 Angiotensin II for the Treatment of High-Output Shock (ATHOS-3) trial to determine whether the addition of angiotensin II to background vasopressors would improve blood pressure in patients with catecholamine-resistant vasodilatory shock.…”

mentioning

confidence: 99%

Angiotensin II for the Treatment of Vasodilatory Shock

Jamme

¹

,

Hertig

²

,

Rafat

³

2017

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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). CONCLUSIONSAngiotensin II effectively increased blood pressure in patients with vasodilatory shock that did not respond to high doses of conventional vasopressors. (Funded by La Jolla Pharmaceutical Company; ATHOS-3 ClinicalTrials.gov number, NCT02338843.) a bs tr ac t

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Angiotensin II in Refractory Septic Shock

Cited by 55 publications

References 55 publications

Angiotensin II for the Treatment of Vasodilatory Shock

Angiotensin II for the Treatment of Vasodilatory Shock

Angiotensin II increases blood pressure in patients with refractory vasodilatory shock

Angiotensin II for the Treatment of Vasodilatory Shock

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