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 language | English |
|---|---|
| Pages (from-to) | 419-430 |
| Number of pages | 12 |
| Journal | New England Journal of Medicine |
| Volume | 377 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 3 Aug 2017 |
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Angiotensin II for the Treatment of Vasodilatory Shock. / Khanna, Ashish; English, Shane; Wang, Xueyuan; Ham, Kealy; Tumlin, James; Szerlip, Harold; Busse, Laurence; Altaweel, Laith; Albertson, Timothy; Mackey, Caleb; McCurdy, Michael; Boldt, David; Chock, Stefan; Young, Paul; Krell, Kenneth; Wunderink, Richard; Ostermann, Marlies; Murugan, Raghavan; Gong, Michelle; Panwar, Rakshit; Hastbacka, Johanna; Favory, Raphael; Thompson, B Taylor; Venkatesh, Balasubramanian; Bellomo, Rinaldo; Jensen, Jeffrey; Kroll, Stew; Chawla, Lakhmir; Tidmarsh, George; Deane, Adam; Foreman, Michael; Garrett, John; Rabeler, Brandon; Mora Jr, Adan; Friedman, Bruce; Shaver, Joseph; Vourlekis, Jason; Djurkovic, Svetolik; Anderson, Sarah; Tanveer, Samer; Ramesh, Swathi; Wang, Jing; King, Christopher; Brannan, Kevin; Zhen, Shu; Smith, Karlie; Southard, Courtney; Landmeier, Mark; Raj, Rishi; Shah, Raj; Russell, Susan; Weiss, Curtis; Galphin, Claude; Poole, Christopher; Shome, Sibaji; Gunter Jr, John; Huang, David; Gunn, Scott; Kim, Hyung; Elmer, Jonathan; Molyneaux, Bradley; Neal, Matthew; Puttarajappa, Chethan; Callaway, Clifton; Al-Khafaji, Ali; Bihorac, Azra; Smith, William; Janelle, Gregory; White, Peggy; Del Rio, J Mauricio; Iboaya, Ehimemen; Al-Hegelan, Mashael; Jimenez, Amanda; Chung, Kevin; Pamplin, Jeremy; Cancio, Leopoldo; Driscoll, Ian; Graybill, John; McCann, Edward; Sams, Valerie; Rizzo, Julie; Rowan, Matthew; Ainsworth, Craig; Kashani, Kianoush; Smischney, Nathan; Iyer, Vivek; Kabler, Heidi; Stucke, Sheri; Campos, Kathleen; Prat, Brenda; Shin, Elliot; Johnson, Matthew; Richardson, Christopher; Fisher, Christopher; MacIntyre, Allan; Kim, Kitae; Feinstein, Daniel; MacQuaid, Douglas; Ramaswamy, Murali; Hoffman, Paul; Desai, Rahul; Rivet, Carly; Yacoub, Wesam; Sessler, Daniel; Protto, Silvia; Sreedharan, Roshni; Liu, Jia; Ayad, Sabry; Elo, Brett; Udeh, Chiedozie; Hite, Duncan; Duggal, Abhijit; Hanane, Tarik; Chodavarapu, Praneeta; Saha, Partha; Schacham, Yehoshua; Yilmaz, Huseyin; Dries, David; Emiru, Tenbit; Brogan, Michael; Bennett, Bruce; Nguyen, H Bryant; Bland, David; Giri, Paresh; Dinh, Vi; Maken, Kanwalijeet; Tan, Laren; Morrissey, Brian; Black, Hugh; Sandrock, Christian; Sebat, Christian; Hou, Peter; Frendl, Gygorgy; Guanaga, Derek; Long, Matthew; Loughlin, Jesse; Gemunden, Sean; Seethla, Raghu; Pentakota, Sujatha; Askari, Reza; Aisiku, Imoigele; Singh, Sumit; Gudzenko, Vadim; Meltzer, Joseph; Chang, Steven; Saggar, Rajan; Barjaktarevic, Igor; Edwards, William; Rolston, Daniel; Hsieh, S Jean; Hope, Aluko; Soto, Graciela; Gershengorn, Hayley; Qadir, Nida; Kordesch, Kristina; Bhatt, Muneer; Gary, Brittany; Chen, Tina; Law, Lawrence; Wu, Chao-Ping; Ataucuri-Vargas, Jorge; Dahn, Cassidy; Koura, Firas; Akers, Lori; Raichel, Michael; Kethireddy, Shravan; Layon, Abraham; Blyler, Kay; Weller, Renee; Bagnata, Linda; Herring, Molly; Snyder, Trudy; Mitchell, Michael; Penupolu, Sudheer; Nealy, Zachariah; Snell, Kenneth; Merkel, Matthias; Treggiari, Miriam; Thornley, Amy; Miller, John; Naum, Chris; Kapoor, Rajat; Pohlman, Timothy; Duncan, Michael; Adams, Heather; Turk, Erin; Oakes, Tessa; Hashmi, Katherine; Broach, Debra; Thorp, Anne-Marie; Strickland, Terri; Logan, Betty; McNamee, Ronda; Nash, Jean; Isaacs, Tonya; Lynn, Caroline; Ferrada, Paula; Anand, Rahul; DeAntonio, Jonathan; Leichtle, Stefan; Strumwasser, Aaron; Grabo, Daniel; Clark, Damon; Biswas, Subaran; Pechulis, Rita; Schwed-Lustgarten, Daniel; Eichelberger, Traci; Knittle, Denise; Strow, Jennifer; Baga, Leslie; Loburak, Sagan; Novak, Jean; Watson, Dorthea; Marsh, Hugh; Hoffman-Huffaker, Shannon; Rovella, Jennifer; Laskosky, Jason; Chodavrapu, Praneet; Harper, Michael; Rice, David; Hasse, Daniel; Zimmermann, Darin; Prekker, Matthew; Leatherman, James; Ambur, Sumanth; Huelster, Joshua; Jacoby, Katherine; Dodd, Kenneth; Soto, Eduardo; Baird, Ian; Cordasco Jr, Edward; Zeno, Brian; Bhullar, Simrit; Lee, Heather; Rudinsky, David; Swiatek, Kevin; Kandiah, Prem; Subramaniam, Ram; Primentel, Cedric; Sadan, Ofer; Killian, Alley; Walsham, James; Krishnan, Anand; Ray, Soumya; Chapman, Andrew; McNamara, Robert; Bennett, Alexander; Bowles, Timothy; Webb, Steven; Bihari, Shailesh.
In: New England Journal of Medicine, Vol. 377, No. 5, 03.08.2017, p. 419-430.Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - Angiotensin II for the Treatment of Vasodilatory Shock
AU - Khanna, Ashish
AU - English, Shane
AU - Wang, Xueyuan
AU - Ham, Kealy
AU - Tumlin, James
AU - Szerlip, Harold
AU - Busse, Laurence
AU - Altaweel, Laith
AU - Albertson, Timothy
AU - Mackey, Caleb
AU - McCurdy, Michael
AU - Boldt, David
AU - Chock, Stefan
AU - Young, Paul
AU - Krell, Kenneth
AU - Wunderink, Richard
AU - Ostermann, Marlies
AU - Murugan, Raghavan
AU - Gong, Michelle
AU - Panwar, Rakshit
AU - Hastbacka, Johanna
AU - Favory, Raphael
AU - Thompson, B Taylor
AU - Venkatesh, Balasubramanian
AU - Bellomo, Rinaldo
AU - Jensen, Jeffrey
AU - Kroll, Stew
AU - Chawla, Lakhmir
AU - Tidmarsh, George
AU - Deane, Adam
AU - Foreman, Michael
AU - Garrett, John
AU - Rabeler, Brandon
AU - Mora Jr, Adan
AU - Friedman, Bruce
AU - Shaver, Joseph
AU - Vourlekis, Jason
AU - Djurkovic, Svetolik
AU - Anderson, Sarah
AU - Tanveer, Samer
AU - Ramesh, Swathi
AU - Wang, Jing
AU - King, Christopher
AU - Brannan, Kevin
AU - Zhen, Shu
AU - Smith, Karlie
AU - Southard, Courtney
AU - Landmeier, Mark
AU - Raj, Rishi
AU - Shah, Raj
AU - Russell, Susan
AU - Weiss, Curtis
AU - Galphin, Claude
AU - Poole, Christopher
AU - Shome, Sibaji
AU - Gunter Jr, John
AU - Huang, David
AU - Gunn, Scott
AU - Kim, Hyung
AU - Elmer, Jonathan
AU - Molyneaux, Bradley
AU - Neal, Matthew
AU - Puttarajappa, Chethan
AU - Callaway, Clifton
AU - Al-Khafaji, Ali
AU - Bihorac, Azra
AU - Smith, William
AU - Janelle, Gregory
AU - White, Peggy
AU - Del Rio, J Mauricio
AU - Iboaya, Ehimemen
AU - Al-Hegelan, Mashael
AU - Jimenez, Amanda
AU - Chung, Kevin
AU - Pamplin, Jeremy
AU - Cancio, Leopoldo
AU - Driscoll, Ian
AU - Graybill, John
AU - McCann, Edward
AU - Sams, Valerie
AU - Rizzo, Julie
AU - Rowan, Matthew
AU - Ainsworth, Craig
AU - Kashani, Kianoush
AU - Smischney, Nathan
AU - Iyer, Vivek
AU - Kabler, Heidi
AU - Stucke, Sheri
AU - Campos, Kathleen
AU - Prat, Brenda
AU - Shin, Elliot
AU - Johnson, Matthew
AU - Richardson, Christopher
AU - Fisher, Christopher
AU - MacIntyre, Allan
AU - Kim, Kitae
AU - Feinstein, Daniel
AU - MacQuaid, Douglas
AU - Ramaswamy, Murali
AU - Hoffman, Paul
AU - Desai, Rahul
AU - Rivet, Carly
AU - Yacoub, Wesam
AU - Sessler, Daniel
AU - Protto, Silvia
AU - Sreedharan, Roshni
AU - Liu, Jia
AU - Ayad, Sabry
AU - Elo, Brett
AU - Udeh, Chiedozie
AU - Hite, Duncan
AU - Duggal, Abhijit
AU - Hanane, Tarik
AU - Chodavarapu, Praneeta
AU - Saha, Partha
AU - Schacham, Yehoshua
AU - Yilmaz, Huseyin
AU - Dries, David
AU - Emiru, Tenbit
AU - Brogan, Michael
AU - Bennett, Bruce
AU - Nguyen, H Bryant
AU - Bland, David
AU - Giri, Paresh
AU - Dinh, Vi
AU - Maken, Kanwalijeet
AU - Tan, Laren
AU - Morrissey, Brian
AU - Black, Hugh
AU - Sandrock, Christian
AU - Sebat, Christian
AU - Hou, Peter
AU - Frendl, Gygorgy
AU - Guanaga, Derek
AU - Long, Matthew
AU - Loughlin, Jesse
AU - Gemunden, Sean
AU - Seethla, Raghu
AU - Pentakota, Sujatha
AU - Askari, Reza
AU - Aisiku, Imoigele
AU - Singh, Sumit
AU - Gudzenko, Vadim
AU - Meltzer, Joseph
AU - Chang, Steven
AU - Saggar, Rajan
AU - Barjaktarevic, Igor
AU - Edwards, William
AU - Rolston, Daniel
AU - Hsieh, S Jean
AU - Hope, Aluko
AU - Soto, Graciela
AU - Gershengorn, Hayley
AU - Qadir, Nida
AU - Kordesch, Kristina
AU - Bhatt, Muneer
AU - Gary, Brittany
AU - Chen, Tina
AU - Law, Lawrence
AU - Wu, Chao-Ping
AU - Ataucuri-Vargas, Jorge
AU - Dahn, Cassidy
AU - Koura, Firas
AU - Akers, Lori
AU - Raichel, Michael
AU - Kethireddy, Shravan
AU - Layon, Abraham
AU - Blyler, Kay
AU - Weller, Renee
AU - Bagnata, Linda
AU - Herring, Molly
AU - Snyder, Trudy
AU - Mitchell, Michael
AU - Penupolu, Sudheer
AU - Nealy, Zachariah
AU - Snell, Kenneth
AU - Merkel, Matthias
AU - Treggiari, Miriam
AU - Thornley, Amy
AU - Miller, John
AU - Naum, Chris
AU - Kapoor, Rajat
AU - Pohlman, Timothy
AU - Duncan, Michael
AU - Adams, Heather
AU - Turk, Erin
AU - Oakes, Tessa
AU - Hashmi, Katherine
AU - Broach, Debra
AU - Thorp, Anne-Marie
AU - Strickland, Terri
AU - Logan, Betty
AU - McNamee, Ronda
AU - Nash, Jean
AU - Isaacs, Tonya
AU - Lynn, Caroline
AU - Ferrada, Paula
AU - Anand, Rahul
AU - DeAntonio, Jonathan
AU - Leichtle, Stefan
AU - Strumwasser, Aaron
AU - Grabo, Daniel
AU - Clark, Damon
AU - Biswas, Subaran
AU - Pechulis, Rita
AU - Schwed-Lustgarten, Daniel
AU - Eichelberger, Traci
AU - Knittle, Denise
AU - Strow, Jennifer
AU - Baga, Leslie
AU - Loburak, Sagan
AU - Novak, Jean
AU - Watson, Dorthea
AU - Marsh, Hugh
AU - Hoffman-Huffaker, Shannon
AU - Rovella, Jennifer
AU - Laskosky, Jason
AU - Chodavrapu, Praneet
AU - Harper, Michael
AU - Rice, David
AU - Hasse, Daniel
AU - Zimmermann, Darin
AU - Prekker, Matthew
AU - Leatherman, James
AU - Ambur, Sumanth
AU - Huelster, Joshua
AU - Jacoby, Katherine
AU - Dodd, Kenneth
AU - Soto, Eduardo
AU - Baird, Ian
AU - Cordasco Jr, Edward
AU - Zeno, Brian
AU - Bhullar, Simrit
AU - Lee, Heather
AU - Rudinsky, David
AU - Swiatek, Kevin
AU - Kandiah, Prem
AU - Subramaniam, Ram
AU - Primentel, Cedric
AU - Sadan, Ofer
AU - Killian, Alley
AU - Walsham, James
AU - Krishnan, Anand
AU - Ray, Soumya
AU - Chapman, Andrew
AU - McNamara, Robert
AU - Bennett, Alexander
AU - Bowles, Timothy
AU - Webb, Steven
AU - Bihari, Shailesh
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.
UR - http://www.scopus.com/inward/record.url?scp=85020839140&partnerID=8YFLogxK
U2 - 10.1056/NEJMoa1704154
DO - 10.1056/NEJMoa1704154
M3 - Article
VL - 377
SP - 419
EP - 430
JO - New England Journal of Medicine
JF - New England Journal of Medicine
SN - 0028-4793
IS - 5
ER -