Angiotensin II for the Treatment of Vasodilatory Shock

Ashish Khanna, Shane English, Xueyuan Wang, Kealy Ham, James Tumlin, Harold Szerlip, Laurence Busse, Laith Altaweel, Timothy Albertson, Caleb Mackey, Michael McCurdy, David Boldt, Stefan Chock, Paul Young, Kenneth Krell, Richard Wunderink, Marlies Ostermann, Raghavan Murugan, Michelle Gong, Rakshit PanwarJohanna Hastbacka, Raphael Favory, B Taylor Thompson, Balasubramanian Venkatesh, Rinaldo Bellomo, Jeffrey Jensen, Stew Kroll, Lakhmir Chawla, George Tidmarsh, Adam Deane, Michael Foreman, John Garrett, Brandon Rabeler, Adan Mora Jr, Bruce Friedman, Joseph Shaver, Jason Vourlekis, Svetolik Djurkovic, Sarah Anderson, Samer Tanveer, Swathi Ramesh, Jing Wang, Christopher King, Kevin Brannan, Shu Zhen, Karlie Smith, Courtney Southard, Mark Landmeier, Rishi Raj, Raj Shah, Susan Russell, Curtis Weiss, Claude Galphin, Christopher Poole, Sibaji Shome, John Gunter Jr, David Huang, Scott Gunn, Hyung Kim, Jonathan Elmer, Bradley Molyneaux, Matthew Neal, Chethan Puttarajappa, Clifton Callaway, Ali Al-Khafaji, Azra Bihorac, William Smith, Gregory Janelle, Peggy White, J Mauricio Del Rio, Ehimemen Iboaya, Mashael Al-Hegelan, Amanda Jimenez, Kevin Chung, Jeremy Pamplin, Leopoldo Cancio, Ian Driscoll, John Graybill, Edward McCann, Valerie Sams, Julie Rizzo, Matthew Rowan, Craig Ainsworth, Kianoush Kashani, Nathan Smischney, Vivek Iyer, Heidi Kabler, Sheri Stucke, Kathleen Campos, Brenda Prat, Elliot Shin, Matthew Johnson, Christopher Richardson, Christopher Fisher, Allan MacIntyre, Kitae Kim, Daniel Feinstein, Douglas MacQuaid, Murali Ramaswamy, Paul Hoffman, Rahul Desai, Carly Rivet, Wesam Yacoub, Daniel Sessler, Silvia Protto, Roshni Sreedharan, Jia Liu, Sabry Ayad, Brett Elo, Chiedozie Udeh, Duncan Hite, Abhijit Duggal, Tarik Hanane, Praneeta Chodavarapu, Partha Saha, Yehoshua Schacham, Huseyin Yilmaz, David Dries, Tenbit Emiru, Michael Brogan, Bruce Bennett, H Bryant Nguyen, David Bland, Paresh Giri, Vi Dinh, Kanwalijeet Maken, Laren Tan, Brian Morrissey, Hugh Black, Christian Sandrock, Christian Sebat, Peter Hou, Gygorgy Frendl, Derek Guanaga, Matthew Long, Jesse Loughlin, Sean Gemunden, Raghu Seethla, Sujatha Pentakota, Reza Askari, Imoigele Aisiku, Sumit Singh, Vadim Gudzenko, Joseph Meltzer, Steven Chang, Rajan Saggar, Igor Barjaktarevic, William Edwards, Daniel Rolston, S Jean Hsieh, Aluko Hope, Graciela Soto, Hayley Gershengorn, Nida Qadir, Kristina Kordesch, Muneer Bhatt, Brittany Gary, Tina Chen, Lawrence Law, Chao-Ping Wu, Jorge Ataucuri-Vargas, Cassidy Dahn, Firas Koura, Lori Akers, Michael Raichel, Shravan Kethireddy, Abraham Layon, Kay Blyler, Renee Weller, Linda Bagnata, Molly Herring, Trudy Snyder, Michael Mitchell, Sudheer Penupolu, Zachariah Nealy, Kenneth Snell, Matthias Merkel, Miriam Treggiari, Amy Thornley, John Miller, Chris Naum, Rajat Kapoor, Timothy Pohlman, Michael Duncan, Heather Adams, Erin Turk, Tessa Oakes, Katherine Hashmi, Debra Broach, Anne-Marie Thorp, Terri Strickland, Betty Logan, Ronda McNamee, Jean Nash, Tonya Isaacs, Caroline Lynn, Paula Ferrada, Rahul Anand, Jonathan DeAntonio, Stefan Leichtle, Aaron Strumwasser, Daniel Grabo, Damon Clark, Subaran Biswas, Rita Pechulis, Daniel Schwed-Lustgarten, Traci Eichelberger, Denise Knittle, Jennifer Strow, Leslie Baga, Sagan Loburak, Jean Novak, Dorthea Watson, Hugh Marsh, Shannon Hoffman-Huffaker, Jennifer Rovella, Jason Laskosky, Praneet Chodavrapu, Michael Harper, David Rice, Daniel Hasse, Darin Zimmermann, Matthew Prekker, James Leatherman, Sumanth Ambur, Joshua Huelster, Katherine Jacoby, Kenneth Dodd, Eduardo Soto, Ian Baird, Edward Cordasco Jr, Brian Zeno, Simrit Bhullar, Heather Lee, David Rudinsky, Kevin Swiatek, Prem Kandiah, Ram Subramaniam, Cedric Primentel, Ofer Sadan, Alley Killian, James Walsham, Anand Krishnan, Soumya Ray, Andrew Chapman, Robert McNamara, Alexander Bennett, Timothy Bowles, Steven Webb, Shailesh Bihari

Research output: Contribution to journalArticle

197 Citations (Scopus)

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
Pages (from-to)419-430
Number of pages12
JournalNew England Journal of Medicine
Volume377
Issue number5
DOIs
Publication statusPublished - 2017

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    Khanna, A., English, S., Wang, X., Ham, K., Tumlin, J., Szerlip, H., Busse, L., Altaweel, L., Albertson, T., Mackey, C., McCurdy, M., Boldt, D., Chock, S., Young, P., Krell, K., Wunderink, R., Ostermann, M., Murugan, R., Gong, M., ... Bihari, S. (2017). Angiotensin II for the Treatment of Vasodilatory Shock. New England Journal of Medicine, 377(5), 419-430. https://doi.org/10.1056/NEJMoa1704154