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Review
. 2018 Jul 26;14:1287-1298.
doi: 10.2147/TCRM.S150434. eCollection 2018.

Angiotensin II: A New Therapeutic Option for Vasodilatory Shock

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Free PMC article
Review

Angiotensin II: A New Therapeutic Option for Vasodilatory Shock

Rachel L Bussard et al. Ther Clin Risk Manag. .
Free PMC article

Abstract

Angiotensin II (Ang II), part of the renin-angiotensin-aldosterone system (RAS), is a potent vasoconstrictor and has been recently approved for use by the US Food and Drug Administration in high-output shock. Though not a new drug, the recently published Angiotensin II for the Treatment of High Output Shock (ATHOS-3) trial, as well as a number of retrospective analyses have sparked renewed interest in the use of Ang II, which may have a role in treating refractory shock. We describe refractory shock, the unique mechanism of action of Ang II, RAS dysregulation in shock, and the evidence supporting the use of Ang II to restore blood pressure. Evidence suggests that Ang II may preferentially be of benefit in acute kidney injury and acute respiratory distress syndrome, where the RAS is known to be disrupted. Additionally, there may be a role for Ang II in cardiogenic shock, angiotensin converting enzyme inhibitor overdose, cardiac arrest, liver failure, and in settings of extracorporeal circulation.

Keywords: catecholamine resistance; refractory shock.

Conflict of interest statement

Disclosure LWB reports receiving consulting fees from La Jolla Pharmaceutical Company. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
The renin–angiotensin–aldosterone system. Notes: Angiotensinogen originates in the liver, is cleaved to angiotensin I by renin in the kidney, and is further cleaved to angiotensin II by ACE, primarily in the lungs. Angiotensin II has a multitude of effects throughout the body, including modulation of sympathetic activity and electrolyte and free water homeostasis. It is also a potent direct vasoconstrictor and potentiates the release of both aldosterone and ADH. Abbreviations: ACE, angiotensin converting enzyme; ADH, antidiuretic hormone.
Figure 2
Figure 2
Progressive Kaplan–Meier analysis of the mortality effect of Ang II in patients with ARDS. Notes: Kaplan–Meier estimate of survival of patients enrolled in the ATHOS-3 study through day 28 by severity of ARDS. In ATHOS-3, patients were randomized to standard of care therapy plus either placebo or Ang II. A post hoc subgroup analysis of patients in ATHOS-3 with ARDS at enrollment showed that the observed mortality benefit of patients receiving Ang II was more pronounced with higher severity of ARDS. (A) Patients with mild ARDS at baseline. (B) Patients with moderate ARDS at baseline. (C) Patients with severe ARDS at baseline. Reproduced from Busse LA, Gong T, Thompson M. Outcomes in patients with acute respiratory distress syndrome receiving angiotensin II for vasodilatory shock. Critical Care. 2018;22(Suppl 1):82. Abbreviations: Ang II, angiotensin II; ARDS, acute respiratory distress syndrome.

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