Abstract
Purpose
Angiotensin II (ATII) is a potent endogenous vasoconstrictor that has recently garnered
regulatory approval for the treatment of distributive shock, including septic shock.
Traditional vasoactive substances used in the management of distributive shock include
norepinephrine, epinephrine, phenylephrine, and vasopressin. However, their use can
be associated with deleterious adverse drug effects, such as splanchnic vasoconstriction
and associated hypoperfusion. The purpose of this review is to describe ATII, including
its pharmacologic mechanisms, pharmacokinetic profile, evidence of efficacy and tolerability,
and potential role in contemporary critical care practice.
Methods
Peer-reviewed clinical trials and relevant treatment guidelines published from 1966
to September 14, 2019, were identified from Medline/PubMed using the following search
terms: angiotensin II OR angiotensin 2 AND shock OR septic shock OR vasodilatory shock. Pertinent review articles were reviewed for additional studies for inclusion and
discussion. The final decision on the inclusion of studies in the current review was
based on the expert opinion of the authors.
Findings
On the basis of the available evidence, ATII is effective at elevating blood pressure
in patients with distributive shock and appears to reduce the dose of concurrent vasopressors
to maintain adequate blood pressure. ATII has been investigated for other causes of
shock; however, robust evidence of off-label indications is lacking and is much needed.
Clinical and cost benefits compared with traditional vasopressors have yet to be established.
Implications
ATII represents a welcome addition to the armamentarium of critical care clinicians.
Enthusiasm for the use of ATII should be balanced with the current gaps in our understanding
of ATII in patients with shock. Until further evidence provides more clinically meaningful
benefits, as well as cost-effectiveness compared with currently available vasopressors,
critical care clinicians should reserve ATII for salvage therapy in patients with
septic shock.
Key words
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Clinical TherapeuticsAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016.Crit Care Med. 2017; 45: 486-552
- Understanding vasoactive medications: focus on pharmacology and effective titration.J Infus Nurs. 2014; 37: 82-86
- Assessment of global incidence and mortality of hospital-treated sepsis. current estimates and limitations.Am J Respir Crit Care Med. 2015; 193: 259-272
- Intravenous angiotensin II for the treatment of high-output shock (ATHOS trial): a pilot study.Crit Care. 2014; 18: 534
- Angiotensin II for the treatment of vasodilatory shock.N Engl J Med. 2017; 377: 419-430
- Outcomes in patients with vasodilatory shock and renal replacement therapy treated with intravenous angiotensin II.Crit Care Med. 2018; 46: 949-957
- A retrospective review of angiotensin II use in adult patients with refractory distributive shock.J Intensive Care Med. 2019 Sep 3; ([Epub ahead of print] Pubmed ID: 31480886)
- Angiotensin in ECMO patients with refractory shock.Crit Care. 2018; 22: 288
- Angiotensin II use in refractory multisystem shock: a case report.Cureus. 2018; 10e3665
- When all else fails: novel use of angiotensin II for vasodilatory shock: a case report.AA Pract. 2018; 11: 175-180
- Synthetic human angiotensin II in pediatric patients with vasodilatory shock: a report on two patients.Crit Care Explorations. 2019; 1e0036
- Angiotensin for septic shock unresponsive to noradrenaline.Arch Dis Child. 2000; 82: 388-389
- The effect of angiotensin II on blood pressure in patients with circulatory shock: a structured review of the literature.Crit Care. 2017; 21: 324
- Synthetic human angiotensin II for postcardiopulmonary bypass vasoplegic shock.J Cardiothorac Vasc Anesth. 2019 Mar 8; 33 ([Epub ahead of print]): 3080-3084
- Use of angiotensin II for post cardiopulmonary bypass vasoplegic syndrome.Ann Thorac Surg. 2018; 108: e5-e7
- Use of angiotensin II for vasoplegic shock in a combined heart and liver transplant recipient with systolic anterior motion physiology.J Cardiothorac Vasc Anesth. 2019; 33: 2366-2367
- Successful treatment of antihypertensive overdose using intravenous angiotensin II.J Emerg Med. 2019 Jul 3; ([Epub ahead of print] Pubmed ID: 31279637)
- Enalapril overdose treated with angiotensin infusion.Lancet. 1993; 341: 703
- Enalapril overdose and the corrective effect of intravenous angiotensin II.Br J Clin Pharmacol. 1995; 40: 103-104
- Angiotensin in critical care.Crit Care. 2018; 22: 69
- Angiotensin II induces plasminogen activator inhibitor-1 and -2 expression in vascular endothelial and smooth muscle cells.J Clin Invest. 1995; 95: 1353-1362
- A blast from the past: revival of angiotensin II for vasodilatory shock.Ann Pharmacother. 2018; 52: 920-927
- Angiotensin II and its metabolites stimulate PAI-1 protein release from human adipocytes in primary culture.Hypertension. 2001; 37: 1336-1340
- Renin-angiotensin system revisited.J Intern Med. 2008; 264: 224-236
- Giapreza (Angiotensin II) [package Insert]. La Jolla Pharmaceutical Company, San Diego, CA2018
- Comparative study of angiotensin and nor-adrenaline in hypotensive states (shock).J Assoc Physicians India. 1966; 14: 639-645
- [First clinical experiences on the use of beta-angiotensin II: treatment of a grave case of shock].Gazz Int Med Chir. 1965; 69: 1557-1560
European Medicines Agency website. Meeting Highlights from the Committee for Medicinal Products for Human Use (CHMP); 24-27 June 2019. https://www.ema.europa.eu/en/news/meeting-highlights-committeemedicinal-products-human-usechmp-24-27-june-2019. Accessed July 1, 2019.
- Sepsis in older adults.Infect Dis Clin North Am. 2017; 31: 731-742
- A study of LJPC-501 in pediatric patients with hypotension.(Available from:)https://ClinicalTrials.gov/show/NCT03431077Date accessed: July 1, 2019
- A study of LJPC-501 in paediatric patients with hypotension associated with distributive or vasodilatory shock.(Available from:)https://ClinicalTrials.gov/show/NCT03623529Date accessed: July 1, 2019
- Initial resuscitation and management of pediatric septic shock.Minerva Pediatr. 2015; 67: 141-158
- Modulation of vascular reactivity after acute calcium antagonist administration in pregnant women moderately sensitive to angiotensin infusion.Boll Soc Ital Biol Sper. 1994; 70: 243-248
- The value of the angiotensin sensitivity test in the early diagnosis of hypertensive disorders in pregnancy.Am J Obstet Gynecol. 1982; 142: 17-20
- Cerebral salt wasting: pathophysiology, diagnosis, and treatment.Neurosurg Clin N Am. 2010; 21: 339-352
- Direct stimulation of angiotensin II type 2 receptor initiated after stroke ameliorates ischemic brain damage.Am J Hypertens. 2014; 27: 1036-1044
- Recent updates in the pharmacological management of sepsis and septic shock: a systematic review focused on fluid resuscitation, vasopressors, and corticosteroids.Ann Pharmacother. 2019; 53: 385-395
- Vasopressin versus norepinephrine infusion in patients with septic shock.N Engl J Med. 2008; 358: 877-887
- Comparison of dopamine and norepinephrine in the treatment of shock.N Engl J Med. 2010; 362: 779-789
- NTAP - GIAPREZA.([online] Available at:)
- NTAP - GIAPREZA.([online] Available at:)
Article info
Publication history
Published online: October 24, 2019
Accepted:
September 24,
2019
Identification
Copyright
© 2019 Elsevier Inc. All rights reserved.
