Outcomes in Patients with Vasodilatory Shock and Renal Replacement Therapy Treated with Intravenous Angiotensin II

Critical Care Medicine - Tập 46 Số 6 - Trang 949-957 - 2018
James A. Tumlin1,2,3, Raghavan Murugan4,1,3, Adam M. Deane5, Marlies Ostermann6,1,3, Laurence W. Busse7, Kealy R. Ham8,9, Kianoush Kashani10,1,3, Harold M. Szerlip11, John R. Prowle12,13,1,3, Azra Bihorac14, Kevin W. Finkel1,15,3, Alexander Zarbock1,3, Lui G. Forni16,1,3, S. Lynch17,1,3, Jeff Jensen17,1,3, Stew Kroll17,1,3, Lakhmir S. Chawla17,1,3, George F. Tidmarsh17,1,3, Rinaldo Bellomo18,19,20,21
1Shannan Lynch, Jeff Jensen, Stew Kroll, Lakhmir Chawla, and George Tidmarsh are employees of La Jolla Pharmaceutical Company. The Angiotensin II for the Treatment of High-Output Shock 3 (ATHOS-3) trial was funded and supported by La Jolla Pharmaceutical Company. All other authors participated in the ATHOS-3 trial as investigators and work(ed) at institutions that were funded by La Jolla Pharmaceutical Company in support of the ATHOS-3 trial. Additionally, John R. Prowle has received consultancy fees and speaker honoraria from Nikkiso Europe GmbH and speaker honoraria from Baxter, Inc. Raghavan Murugan was awarded a research grant from La Jolla Pharmaceutical Company, and has received consulting fees from Beckman and Coulter, Inc and Bioporto, Inc. Kianoush Kashani has received a travel grant from La Jolla Pharmaceutical Company for the ATHOS-3 investigator meeting. Marlies Ostermann has received research funding and speaker honoraria from Fresenius Medical Care. Alexander Zarbock has received consulting fees from Astellas and Quark Pharmaceutical
2University of Tennessee College of Medicine, Chattanooga TN.
3speaker honoraria from Astute Medical, Baxter, Frensenius, and Braun
4Department of Critical Care Medicine, and Clinical and Translational Science, Center for Critical Care Nephrology, CRISMA, University of Pittsburgh School of Medicine, Pittsburgh, PA.
5Intensive Care Unit, Royal Melbourne Hospital, University of Melbourne, Grattan St, Parkville, Victoria, VIC, Australia.
6King’s College London, Guy’s & St Thomas’ Hospital, London, UK
7Emory University Department of Medicine, Atlanta, Ga
8University of Minnesota Medical School***
9University of Minnesota Medical School; Department Chair of Critical Care Medicine, Regions Hospital, Saint Paul, MN.
10Division of Nephrology and Hypertension, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Mayo Clinic, Rochester, MN.
11Baylor University Medical Center, Dallas, TX
12Adult Critical Care Unit, Department of Renal and Transplant Medicine, The Royal London Hospital, London, UK
13Adult Critical Care Unit, Department of Renal and Transplant Medicine, The Royal London Hospital, London, UK; William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, UK.
14Division of Nephrology, Hypertension, & Renal Transplantation, Department of Medicine, University of Florida, Gainesville, FL.
15University of Texas Health Science Center at Houston, Houston, TX
16Department of Clinical & Experimental Medicine, Faculty of Health Sciences, University of Surrey & Critical Care Unit, Royal Surrey County Hospital, Guildford, UK.
17La Jolla Pharmaceutical Company.
18Austin Hospital, Heidelberg, VIC, Australia
19Department of Intensive Care, Royal Melbourne Hospital, Melbourne, VIC, Australia.
20The University of Melbourne, Melbourne, VIC, Australia
21The University of Melbourne, Melbourne, VIC, Australia; Austin Hospital, Heidelberg, VIC, Australia; Department of Intensive Care, Royal Melbourne Hospital, Melbourne, VIC, Australia; Australian and New Zealand Intensive Care Research Centre, Melbourne, VIC, Australia.

Tóm tắt

Objective: Acute kidney injury requiring renal replacement therapy in severe vasodilatory shock is associated with an unfavorable prognosis. Angiotensin II treatment may help these patients by potentially restoring renal function without decreasing intrarenal oxygenation. We analyzed the impact of angiotensin II on the outcomes of acute kidney injury requiring renal replacement therapy. Design: Post hoc analysis of the Angiotensin II for the Treatment of High-Output Shock 3 trial. Setting: ICUs. Patients: Patients with acute kidney injury treated with renal replacement therapy at initiation of angiotensin II or placebo (n = 45 and n = 60, respectively). Interventions: IV angiotensin II or placebo. Measurements and Main Results: Primary end point: survival through day 28; secondary outcomes included renal recovery through day 7 and increase in mean arterial pressure from baseline of ≥ 10 mm Hg or increase to ≥ 75 mm Hg at hour 3. Survival rates through day 28 were 53% (95% CI, 38%–67%) and 30% (95% CI, 19%–41%) in patients treated with angiotensin II and placebo (p = 0.012), respectively. By day 7, 38% (95% CI, 25%–54%) of angiotensin II patients discontinued RRT versus 15% (95% CI, 8%–27%) placebo (p = 0.007). Mean arterial pressure response was achieved in 53% (95% CI, 38%–68%) and 22% (95% CI, 12%–34%) of patients treated with angiotensin II and placebo (p = 0.001), respectively. Conclusions: In patients with acute kidney injury requiring renal replacement therapy at study drug initiation, 28-day survival and mean arterial pressure response were higher, and rate of renal replacement therapy liberation was greater in the angiotensin II group versus the placebo group. These findings suggest that patients with vasodilatory shock and acute kidney injury requiring renal replacement therapy may preferentially benefit from angiotensin II.

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Critical Care Medicine

Tập 46 Số 6

949-957

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