Angiotensin II: a new therapeutic option for vasodilatory shock

Figures & data

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 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):82.¹³¹
Abbreviations: Ang II, angiotensin II; ARDS, acute respiratory distress syndrome.

Table 1 Current and contemplated uses of Ang II

Disease state	Properties of Ang II providing benefit	Status of use/evidence
High-output shock	Direct vasoconstriction, catecholamine sparing	Approved for clinical use based on two RCTs (Chawla et al, 2016^Citation27; Khanna et al, 2017^Citation36)
Cardiogenic shock	Vasoconstriction, inotropy	Use supported by retrospective data (Busse et al, 2017^Citation6)
Cardiac arrest	Vasopressor effect, improved contractility, increased coronary perfusion, catecholamine potentiation	Use supported by retrospective data (Busse et al, 2017^Citation6)
Sepsis-induced AKI	Restored glomerular perfusion pressure via efferent vasoconstriction	Evaluated in post hoc analysis of ATHOS-3 RCT (Tumlin, 2018^Citation34)
Shock and ARDS	Vasopressor effect, replacement of Ang II thought to be deficient due to ACE dysfunction or deficiency	Evaluated in post hoc analysis of ATHOS-3 RCT (Busse et al, 2018^Citation121)
ACE inhibitor overdose	Vasopressor effect, replacement of Ang II thought to be deficient due to ACE inhibitors	Use supported by retrospective data (Trilli et al, 1994^Citation88; Jackson et al, 1993^Citation86; Newby et al, 1995^Citation87)
Shock and liver failure	Vasopressor effect, replacement of Ang II thought to be deficient due to reduced angiotensinogen synthesis	Not yet studied
Shock and CPB/ECMO	Vasopressor effect, replacement of Ang II thought to be deficient due to reduced pulmonary circulation	Not yet studied

Abbreviations: ACE, angiotensin converting enzyme; AKI, acute kidney injury; Ang II, angiotensin II; ARDS, acute respiratory distress syndrome; ATHOS-3, Angiotensin II for the Treatment of Vasodilatory Shock; CPB, cardiopulmonary bypass; ECMO, extracorporeal membrane oxygenation; RCT, randomized controlled trial.

BusseLAGongTThompsonMOutcomes in patients with acute respiratory distress syndrome receiving angiotensin II for vasodilatory shockCritical Care201822Suppl 182

 Google Scholar

ChawlaLSBusseLBrasha-MitchellEIntravenous angiotensin II for the treatment of high-output shock (ATHOS trial): a pilot studyCritical Care201418553425286986

 PubMed Web of Science ®Google Scholar

KhannaAEnglishSWWangXSAngiotensin II for the Treatment of Vasodilatory ShockN Engl J Med Overseas Ed20173775419430

 PubMed Web of Science ®Google Scholar

BusseLWMccurdyMTAliOHallAChenHOstermannMThe effect of angiotensin II on blood pressure in patients with circulatory shock: a structured review of the literatureCritical Care201721132429282149

 PubMed Web of Science ®Google Scholar

TumlinJAMuruganRDeaneAMOutcomes in Patients with Vasodilatory Shock and Renal Replacement Therapy Treated with Intravenous Angiotensin IICrit Care Med201846694995729509568

 PubMed Web of Science ®Google Scholar

BusseLAGongTThompsonMOutcomes in patients with acute respiratory distress syndrome receiving angiotensin II for vasodilatory shockCritical Care201822Suppl 182

 Google Scholar

TrilliLEJohnsonKALisinopril Overdose and Management with Intravenous Angiotensin IIAnn Pharmacother19942810116511687841571

 PubMed Web of Science ®Google Scholar

JacksonTCorkeCAgarJEnalapril overdose treated with angiotensin infusionThe Lancet19933418846703

 Web of Science ®Google Scholar

NewbyDELeeMRGrayAJBoonNAEnalapril overdose and the corrective effect of intravenous angiotensin II [letter]Br J Clin Pharmacol19954011031048527259

 PubMed Web of Science ®Google Scholar