Angiotensin II for the treatment of vasodilatory shock

Ashish Khanna, Shane W. English, Xueyuan S. Wang, Kealy Ham, James Tumlin, Harold Szerlip, Laurence W. Busse, Laith Altaweel, Timothy E. Albertson, Caleb Mackey, Michael T. McCurdy, David W. Boldt, Stefan Chock, Paul J. Young, Kenneth Krell, Richard G. Wunderink, Marlies Ostermann, Raghavan Murugan, Michelle Ng Gong, Rakshit PanwarJohanna Htbacka, Raphael Favory, Balasubramanian Venkatesh, B. Taylor Thompson, Rinaldo Bellomo, Jeffrey Jensen, Stew Kroll, Lakhmir S. Chawla, George F. Tidmarsh

Research output: Contribution to journalArticle

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Abstract

BACKGROUND Vasodilatory 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. METHODS We 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. RESULTS A 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 Angiotensin II effectively increased blood pressure in patients with vasodilatory shock that did not respond to high doses of conventional vasopressors.

Original languageEnglish (US)
Pages (from-to)419-430
Number of pages12
JournalNew England Journal of Medicine
Volume377
Issue number5
DOIs
StatePublished - Aug 3 2017

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Angiotensin II
Shock
Placebos
Therapeutics
Confidence Intervals
Organ Dysfunction Scores
Norepinephrine
Arterial Pressure
Odds Ratio
Body Weight
Blood Pressure
Mortality

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Khanna, A., English, S. W., Wang, X. S., Ham, K., Tumlin, J., Szerlip, H., ... Tidmarsh, G. F. (2017). Angiotensin II for the treatment of vasodilatory shock. New England Journal of Medicine, 377(5), 419-430. https://doi.org/10.1056/NEJMoa1704154

Angiotensin II for the treatment of vasodilatory shock. / Khanna, Ashish; English, Shane W.; Wang, Xueyuan S.; Ham, Kealy; Tumlin, James; Szerlip, Harold; Busse, Laurence W.; Altaweel, Laith; Albertson, Timothy E.; Mackey, Caleb; McCurdy, Michael T.; Boldt, David W.; Chock, Stefan; Young, Paul J.; Krell, Kenneth; Wunderink, Richard G.; Ostermann, Marlies; Murugan, Raghavan; Gong, Michelle Ng; Panwar, Rakshit; Htbacka, Johanna; Favory, Raphael; Venkatesh, Balasubramanian; Taylor Thompson, B.; Bellomo, Rinaldo; Jensen, Jeffrey; Kroll, Stew; Chawla, Lakhmir S.; Tidmarsh, George F.

In: New England Journal of Medicine, Vol. 377, No. 5, 03.08.2017, p. 419-430.

Research output: Contribution to journalArticle

Khanna, A, English, SW, Wang, XS, Ham, K, Tumlin, J, Szerlip, H, Busse, LW, Altaweel, L, Albertson, TE, Mackey, C, McCurdy, MT, Boldt, DW, Chock, S, Young, PJ, Krell, K, Wunderink, RG, Ostermann, M, Murugan, R, Gong, MN, Panwar, R, Htbacka, J, Favory, R, Venkatesh, B, Taylor Thompson, B, Bellomo, R, Jensen, J, Kroll, S, Chawla, LS & Tidmarsh, GF 2017, 'Angiotensin II for the treatment of vasodilatory shock', New England Journal of Medicine, vol. 377, no. 5, pp. 419-430. https://doi.org/10.1056/NEJMoa1704154
Khanna A, English SW, Wang XS, Ham K, Tumlin J, Szerlip H et al. Angiotensin II for the treatment of vasodilatory shock. New England Journal of Medicine. 2017 Aug 3;377(5):419-430. https://doi.org/10.1056/NEJMoa1704154
Khanna, Ashish ; English, Shane W. ; Wang, Xueyuan S. ; Ham, Kealy ; Tumlin, James ; Szerlip, Harold ; Busse, Laurence W. ; Altaweel, Laith ; Albertson, Timothy E. ; Mackey, Caleb ; McCurdy, Michael T. ; Boldt, David W. ; Chock, Stefan ; Young, Paul J. ; Krell, Kenneth ; Wunderink, Richard G. ; Ostermann, Marlies ; Murugan, Raghavan ; Gong, Michelle Ng ; Panwar, Rakshit ; Htbacka, Johanna ; Favory, Raphael ; Venkatesh, Balasubramanian ; Taylor Thompson, B. ; Bellomo, Rinaldo ; Jensen, Jeffrey ; Kroll, Stew ; Chawla, Lakhmir S. ; Tidmarsh, George F. / Angiotensin II for the treatment of vasodilatory shock. In: New England Journal of Medicine. 2017 ; Vol. 377, No. 5. pp. 419-430.
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abstract = "BACKGROUND Vasodilatory 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. METHODS We 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. RESULTS A 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 Angiotensin II effectively increased blood pressure in patients with vasodilatory shock that did not respond to high doses of conventional vasopressors.",
author = "Ashish Khanna and English, {Shane W.} and Wang, {Xueyuan S.} and Kealy Ham and James Tumlin and Harold Szerlip and Busse, {Laurence W.} and Laith Altaweel and Albertson, {Timothy E.} and Caleb Mackey and McCurdy, {Michael T.} and Boldt, {David W.} and Stefan Chock and Young, {Paul J.} and Kenneth Krell and Wunderink, {Richard G.} and Marlies Ostermann and Raghavan Murugan and Gong, {Michelle Ng} and Rakshit Panwar and Johanna Htbacka and Raphael Favory and Balasubramanian Venkatesh and {Taylor Thompson}, B. and Rinaldo Bellomo and Jeffrey Jensen and Stew Kroll and Chawla, {Lakhmir S.} and Tidmarsh, {George F.}",
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T1 - Angiotensin II for the treatment of vasodilatory shock

AU - Khanna, Ashish

AU - English, Shane W.

AU - Wang, Xueyuan S.

AU - Ham, Kealy

AU - Tumlin, James

AU - Szerlip, Harold

AU - Busse, Laurence W.

AU - Altaweel, Laith

AU - Albertson, Timothy E.

AU - Mackey, Caleb

AU - McCurdy, Michael T.

AU - Boldt, David W.

AU - Chock, Stefan

AU - Young, Paul J.

AU - Krell, Kenneth

AU - Wunderink, Richard G.

AU - Ostermann, Marlies

AU - Murugan, Raghavan

AU - Gong, Michelle Ng

AU - Panwar, Rakshit

AU - Htbacka, Johanna

AU - Favory, Raphael

AU - Venkatesh, Balasubramanian

AU - Taylor Thompson, B.

AU - Bellomo, Rinaldo

AU - Jensen, Jeffrey

AU - Kroll, Stew

AU - Chawla, Lakhmir S.

AU - Tidmarsh, George F.

PY - 2017/8/3

Y1 - 2017/8/3

N2 - BACKGROUND Vasodilatory 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. METHODS We 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. RESULTS A 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 Angiotensin II effectively increased blood pressure in patients with vasodilatory shock that did not respond to high doses of conventional vasopressors.

AB - BACKGROUND Vasodilatory 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. METHODS We 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. RESULTS A 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 Angiotensin II effectively increased blood pressure in patients with vasodilatory shock that did not respond to high doses of conventional vasopressors.

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