What is the role of Angiotensin II (Angiotensin 2) in treating hypotension (shock)?

From the Guidelines

Angiotensin II is recommended as a vasopressor option for patients with refractory shock who remain hypotensive despite adequate fluid resuscitation and first-line vasopressors. The use of Angiotensin II in treating hypotension (shock) is supported by recent studies, including a narrative review by a multidisciplinary panel of experts published in Intensive Care Medicine in 2018 1. This review highlights the importance of vasoactive drugs in shock management and suggests that Angiotensin II may be useful due to its norepinephrine-sparing effects.

Key Points to Consider

• Angiotensin II works by directly stimulating AT1 receptors, causing potent vasoconstriction and increasing blood pressure 1.
• It is particularly useful in vasodilatory shock states and may be beneficial in patients with acute kidney injury.
• When implementing Angiotensin II therapy, blood pressure should be monitored continuously, and the dose should be decreased once the target blood pressure is maintained for 30 minutes.
• Potential adverse effects include thromboembolism, peripheral ischemia, and digital necrosis, so patients should be monitored for these complications 1.
• Angiotensin II should be used cautiously in patients with thrombotic conditions or receiving other vasopressors, and it should be tapered gradually to avoid rebound hypotension.

Dosage and Administration

• The typical starting dose of Angiotensin II is 20 ng/kg/min administered as a continuous IV infusion.
• The dose can be titrated every 5 minutes by increments of up to 15 ng/kg/min as needed to achieve target blood pressure.
• The maximum dose is 80 ng/kg/min during the first 3 hours and 40 ng/kg/min for maintenance.

Clinical Considerations

• The use of Angiotensin II in pediatric and neonatal septic shock is also supported by clinical practice parameters published in Critical Care Medicine in 2009 1.
• In these cases, Angiotensin II can be used in conjunction with other vasoactive agents, such as norepinephrine and vasopressin, to restore blood pressure.
• However, the use of these potent vasoconstrictors requires careful monitoring of cardiac output and systemic vascular resistance to avoid reducing cardiac output.

From the FDA Drug Label

12.1. Mechanism of Action Angiotensin II raises blood pressure by vasoconstriction and increased aldosterone release. For the 114 (70%) patients in the GIAPREZA arm who reached the target MAP at Hour 3, the median time to reach the target MAP endpoint was approximately 5 minutes.

The role of Angiotensin II in treating hypotension (shock) is to raise blood pressure by vasoconstriction and increased aldosterone release. This is achieved through the direct action of angiotensin II on the vessel wall, mediated by binding to the G-protein-coupled angiotensin II receptor type 1 on vascular smooth muscle cells. The effect of Angiotensin II on blood pressure is rapid, with a median time to reach the target Mean Arterial Pressure (MAP) endpoint of approximately 5 minutes 2.

• Key Points:
  • Angiotensin II raises blood pressure by vasoconstriction and increased aldosterone release
  • Rapid effect on blood pressure, with a median time to reach target MAP endpoint of approximately 5 minutes
  • Used in the treatment of hypotension (shock) that is refractory to other vasopressors 2, 2

From the Research

Role of Angiotensin II in Treating Hypotension (Shock)

• Angiotensin II is a potent vasoconstrictor that has been approved as an add-on vasopressor in vasodilatory shock 3, 4.
• It has been shown to increase blood pressure and reduce the dose of concurrent vasopressors in patients with distributive shock, including septic shock 3, 4, 5.
• Angiotensin II has a rapid effect, with target mean arterial pressure (MAP) obtained within 30 minutes in most patients 5.
• It is effective in reducing catecholamine dose significantly, and its use should be considered when target MAP cannot be achieved with conventional vasopressors 5.
• Angiotensin II may be of particular benefit in patients with refractory shock due to certain drug overdoses, such as combined lisinopril and amlodipine overdose 6.
• Its role in patients after orthotopic heart transplant or ventricular assist device (VAD) implantation is not well studied, but it has been used in various clinical settings for distributive shock 7.

Clinical Efficacy and Safety

• Several studies, including a large randomized controlled trial, have demonstrated the ability of angiotensin II to increase blood pressure with catecholamine-sparing effects 3, 4, 5.
• Angiotensin II has been shown to be effective in elevating blood pressure in patients with distributive shock and appears to reduce the dose of concurrent vasopressors to maintain adequate blood pressure 4, 5.
• The safety profile of angiotensin II is generally favorable, but clinical and cost benefits compared with traditional vasopressors have yet to be established 4.

Future Perspectives

• Further research is needed to establish the clinical and cost benefits of angiotensin II compared with traditional vasopressors 4.
• Angiotensin II represents a welcome addition to the armamentarium of critical care clinicians, but enthusiasm for its use should be balanced with the current gaps in understanding its role in patients with shock 4.