Angiotensin II for Low Blood Pressure During Surgery

Overseen By Thomas Templeton, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Wake Forest University Health Sciences

Must be taking: Ace inhibitors, Arbs

Disqualifiers: Obesity, Stroke, Heart failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: up to 1 hour

31 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, since it includes patients already on certain blood pressure medications, you might be able to continue them. Please confirm with the trial coordinators.

What data supports the effectiveness of the drug Angiotensin II (Giapreza) for treating low blood pressure during surgery?

A case report showed that Angiotensin II (Giapreza) improved blood pressure in a patient with severe low blood pressure due to a drug overdose, suggesting it can help manage low blood pressure in challenging situations. ^{1 2 3 4 5}

Is Angiotensin II safe for use in humans during surgery?

There is limited safety data specifically for Angiotensin II during surgery, but related drugs acting on the renin-angiotensin system have been associated with low blood pressure during surgery. Some guidelines suggest stopping these drugs before surgery to avoid this risk, but the evidence is not definitive. ^{1 5 6 7 8}

How is the drug Angiotensin II (Giapreza) different from other treatments for low blood pressure during surgery?

Angiotensin II (Giapreza) is unique because it is a novel vasopressor (a drug that raises blood pressure) that can be used when other standard vasopressors are not effective, particularly in cases of vasodilatory shock. It works by directly constricting blood vessels, which can help improve blood pressure and reduce the need for other medications. ^{1 2 9 10 11}

What is the purpose of this trial?

Hypotension in adult patients undergoing general anesthesia is common. This can lead to hypoperfusion of vital organs, organ damage, and states of increased metabolic duress. This may be worse in patients with underlying essential hypertension and worse in patients taking Angiotensin Converting Enzyme Inhibitors (ACE) and Angiotensin Receptor Blockers (ARBs). Intravenous (IV) administration of Ang II may be an effective treatment of hypotension in this patient population.

Research Team

Rohesh Fernando, MD

Principal Investigator

Wake Forest University Health Sciences

Eligibility Criteria

This trial is for adults with high blood pressure who are undergoing general anesthesia and have been treated with blood pressure medications, including ACE inhibitors or ARBs, for over two months. It's not suitable for individuals with asthma, severe obesity (BMI > 40), pregnant women, those with a history of serious heart or lung conditions, stroke, deep vein thrombosis or difficult airways.

Inclusion Criteria

I will be put to sleep for surgery.

I have been treated for high blood pressure with medication for over 2 months.

Exclusion Criteria

I have chronic obstructive pulmonary disease.

I have had a heart attack or have cardiac stents.

You have a hard time breathing.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intravenous (IV) administration of Angiotensin II to manage hypotension during general anesthesia

up to 1 hour

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Angiotensin II

Trial Overview The study is testing the effectiveness of intravenous Angiotensin II as a treatment for low blood pressure that occurs during general anesthesia in patients who already have high blood pressure and are on certain medications.

Participant Groups

Group I: Participants on ARBs Experimental Treatment 1 Intervention

Participants taking ARBs (angiotensin-receptor blockers) will be placed into this group. Intervention: Drug: Angiotensin II.

Group II: Participants on ACE inhibitors Experimental Treatment 1 Intervention

Participants taking ACE inhibitors (angiotensin-converting enzyme inhibitors)will be placed into this group. Intervention: Drug: Angiotensin II.

Group III: Other Classes of Antihypertensive Agents Experimental Treatment 1 Intervention

Participants taking any other class of Antihypertensive Agents will be placed into this group. Intervention: Drug: Angiotensin II.

Angiotensin II is already approved in United States for the following indications:

Approved in United States as Giapreza for:

• Septic shock
• Vasodilatory shock

Who Is Running the Clinical Trial?

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Findings from Research

Patients receiving renin angiotensin antagonists (RAA) during elective surgeries had a significantly higher incidence of intraoperative hypotension (76.0% vs 45.9%) and acute kidney injury (11.6% vs 1.6%) compared to those not on RAA, indicating potential safety concerns.

The study also found that RAA use was associated with a higher rate of major adverse cardiac or cerebrovascular events (6.2% vs 0%), suggesting that RAA may increase the risk of serious complications during surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of renin angiotensin antagonists with adverse perioperative events in patients undergoing elective orthopaedic surgery: a case-control study. Zainudheen, A., Scott, IA., Caney, X.[2018]

Angiotensin II (Giapreza) was successfully used to treat vasodilation caused by a tricyclic overdose, improving hemodynamic parameters in the patient.

This novel application of angiotensin II may allow for lower doses of other vasopressors, potentially enhancing patient outcomes in cases of vasodilatory shock.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Patient With Tricyclic Antidepressant Overdose With Catecholamine-Resistant Hypotension Rescued With Angiotensin II: A Case Report. Ferdowsali, J., Ferdowsali, K.[2021]

A single oral dose of captopril significantly reduced blood pressure in 26 patients with renovascular disease, indicating its effectiveness as an acute angiotensin-converting enzyme (ACE) inhibitor.

The blood pressure response to captopril was predictive of postoperative outcomes, with a strong correlation between preoperative captopril-induced blood pressure changes and postoperative blood pressure levels, suggesting it could be a useful tool for anticipating surgical results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute response to captopril as a predictive test for surgery in renovascular hypertension. Salvetti, A., Arzilli, F., Nuccorini, A., et al.[2018]

Omitting the final preoperative dose of angiotensin-converting enzyme inhibitors (ACEIs) significantly reduced the occurrence of intraoperative hypotension in patients undergoing noncardiac, nonvascular surgeries, with a decrease from 69% in the continuation group to 55% in the omission group.

While the omission of ACEIs led to fewer intraoperative hypotensive events, it also resulted in a higher incidence of postoperative hypertensive episodes, indicating a need for careful management of blood pressure after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective Randomized Evaluation of Preoperative Angiotensin-Converting Enzyme Inhibition (PREOP-ACEI). Shiffermiller, JF., Monson, BJ., Vokoun, CW., et al.[2019]

Acute blockade of B2 receptors using icatibant significantly prevents blood pressure drops in mice treated with angiotensin-converting enzyme inhibitors during hemorrhagic shock, indicating a potential protective mechanism.

The study shows that B2 receptor blockade can rapidly and effectively mitigate the harmful hemodynamic effects associated with angiotensin-converting enzyme inhibitor treatment, which could be beneficial for patients undergoing emergency anesthesia or resuscitation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute Bradykinin Receptor Blockade During Hemorrhagic Shock in Mice Prevents the Worsening Hypotensive Effect of Angiotensin-Converting Enzyme Inhibitor. Charbonneau, H., Buléon, M., Minville, V., et al.[2018]

Patients treated with angiotensin II receptor antagonists (ARA) experienced significantly higher rates of hypotension after anesthesia induction compared to those treated with beta-blockers/calcium channel blockers (BB/CB) or angiotensin-converting enzyme inhibitors (ACEI), with all 12 ARA patients experiencing hypotension.

The ARA group required more ephedrine to manage hypotension and had cases of refractory hypotension that were successfully treated with a vasopressin system agonist, highlighting the need for careful management of blood pressure in these patients during surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The hemodynamic effects of anesthetic induction in vascular surgical patients chronically treated with angiotensin II receptor antagonists. Brabant, SM., Bertrand, M., Eyraud, D., et al.[2022]

The study involving 208 isolated human internal mammary artery rings from 64 patients showed that the angiotensin receptor antagonist GR117289C can induce significant relaxation in arteries precontracted by angiotensin II, suggesting its potential to alleviate graft spasm during coronary artery bypass surgery.

GR117289C demonstrated a noncompetitive blockade of the AT1 receptor and also showed significant relaxation effects on arteries contracted by U46619, indicating it may also affect the thromboxane A2 receptor, making it a promising alternative treatment for graft spasm.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of vasoconstriction by angiotensin receptor antagonist GR117289C in arterial grafts. Liu, MH., Floten, HS., Furnary, AP., et al.[2019]

In a study of 756 surgical patients, chronic use of agents acting on the renin-angiotensin system (ARAS) was not linked to increased episodes of intraoperative hypotension, suggesting that continuing ARAS medication may be safe during surgery.

The study found that while intraoperative hypertension was more common in patients taking ARAS, there was no significant difference in hypotension episodes between those who stopped ARAS before surgery and those who continued it, indicating that the current recommendation for transient discontinuation may need reevaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic utilization of agents acting on the renin-angiotensin system and intraoperative arterial pressure. Castanheira, L., de Lurdes Castro, M., Calheiros, J.[2013]

Continuing angiotensin-converting enzyme (ACE) inhibitor therapy on the day of surgery can lead to significant intraoperative hypotension, as demonstrated by a case where a patient experienced cardiac arrest after taking her medication before surgery.

In a subsequent surgery with the same anesthetic management, withholding blood pressure medications on the day of surgery prevented hypotension, highlighting the importance of managing these medications to ensure patient safety during surgical procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraoperative cardiac arrest: was it the ACE inhibitor? Bjerregaard, J., Jaffe, RA.[2014]

In a study of 14 patients with severe hypotension during anesthetic induction, an intravenous bolus of 2.5 micrograms of angiotensin II effectively increased systolic arterial pressure from 78 mm Hg to 152 mm Hg within 60 seconds.

While angiotensin II successfully restored blood pressure, it also caused a temporary impairment in left ventricular function, indicated by changes in heart metrics such as end-diastolic area and fiber-shortening velocity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treating anesthesia-induced hypotension by angiotensin II in patients chronically treated with angiotensin-converting enzyme inhibitors. Eyraud, D., Mouren, S., Teugels, K., et al.[2019]

Angiotensin II, a newly approved vasopressor, was successfully used to treat a patient with post-cardiopulmonary bypass vasoplegic syndrome who did not respond to standard vasopressors and other treatments.

The patient showed significant improvement, being extubated within 24 hours and meeting important recovery metrics, highlighting the efficacy of Angiotensin II in severe cases of vasodilatory shock.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of Angiotensin II for Post Cardiopulmonary Bypass Vasoplegic Syndrome. Evans, A., McCurdy, MT., Weiner, M., et al.[2019]

References

1. Australia pubmed.ncbi.nlm.nih.gov

Association of renin angiotensin antagonists with adverse perioperative events in patients undergoing elective orthopaedic surgery: a case-control study. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

A Patient With Tricyclic Antidepressant Overdose With Catecholamine-Resistant Hypotension Rescued With Angiotensin II: A Case Report. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Acute response to captopril as a predictive test for surgery in renovascular hypertension. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Prospective Randomized Evaluation of Preoperative Angiotensin-Converting Enzyme Inhibition (PREOP-ACEI). [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Acute Bradykinin Receptor Blockade During Hemorrhagic Shock in Mice Prevents the Worsening Hypotensive Effect of Angiotensin-Converting Enzyme Inhibitor. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

The hemodynamic effects of anesthetic induction in vascular surgical patients chronically treated with angiotensin II receptor antagonists. [2022]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Inhibition of vasoconstriction by angiotensin receptor antagonist GR117289C in arterial grafts. [2019]

8. Italy pubmed.ncbi.nlm.nih.gov

Chronic utilization of agents acting on the renin-angiotensin system and intraoperative arterial pressure. [2013]

9. United States pubmed.ncbi.nlm.nih.gov

Intraoperative cardiac arrest: was it the ACE inhibitor? [2014]

10. United States pubmed.ncbi.nlm.nih.gov

Treating anesthesia-induced hypotension by angiotensin II in patients chronically treated with angiotensin-converting enzyme inhibitors. [2019]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Use of Angiotensin II for Post Cardiopulmonary Bypass Vasoplegic Syndrome. [2019]