Angiotensin II in General Anesthesia

Study Overview
=================
Brief Summary
-----------------
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.

Detailed Description
-----------------
Hypotension in adult patients undergoing general anesthesia is common. Many of the body's normal mechanisms to maintain adequate blood pressure in the non-anesthetized state are significantly altered by anesthetic agents, which may lead to hypotension. This can lead to hypoperfusion of vital organs, organ damage, and states of increased metabolic duress. In response to this it has become standard of care to attempt to maintain blood pressure levels within 20% of baseline in most patients under anesthesia. Maintaining the baseline blood pressure is important as patients may have pathology such as coronary artery disease, carotid stenosis, and renal artery stenosis, and hypotension may compromise the perfusion of these organs. Vasodilation also plays a key role in hypotension due to general anesthesia. Therefore, the intravenous (IV) administration of Ang II may be an effective treatment of hypotension in this patient population.The objective of this study is to determine the infusion rate of Ang II that is necessary to return systolic blood pressure (SBP) to within 5% of baseline or greater in patients with essential hypertension taking ACE inhibitors, ARBs, or different classes of antihypertensive agents and further to determine the plasma levels of different RAAS components

Official Title
-----------------
A Dose Finding Trial for Angiotensin II in Hypertensive Adults on Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers With Anesthesia-Mediated Hypotension

Conditions
-----------------
Hypertension

Intervention / Treatment
-----------------
* Drug: Angiotensin II


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of hypertension and treatment with at least one medication including an ACE inhibitor, ARB, and other agents for greater than 2 months Patients undergoing general anesthesia Exclusion Criteria: BMI > 40 History of deep venous thrombosis / thromboembolic disease History of stroke, Baseline SBP of ≥ 160 mmHg, History of myocardial infarction or cardiac stents Difficult airway Asthma Congestive heart failure Chronic obstructive pulmonary disease Pregnant patients

Ages Eligible for Study
-----------------
Minimum Age: 40 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Participants on ACE inhibitors<br>Participants taking ACE inhibitors (angiotensin-converting enzyme inhibitors)will be placed into this group. Intervention: Drug: Angiotensin II. | Drug: Angiotensin II<br>* Participants in the ACE inhibitors, ARBs, and Other Classes of Antihypertensive Agents who's systolic blood pressure (SBP) is less than 80% of the baseline reading is detected, will have Ang II initiated at 2 ng/kg/min through a peripheral IV. The infusion will be increased at the discretion of the clinical team based on the response of the patient until a SBP within 5% of the baseline SBP.<br>* Other names: Giapreza;|
| Experimental: Participants on ARBs<br>Participants taking ARBs (angiotensin-receptor blockers) will be placed into this group. Intervention: Drug: Angiotensin II. | Drug: Angiotensin II<br>* Participants in the ACE inhibitors, ARBs, and Other Classes of Antihypertensive Agents who's systolic blood pressure (SBP) is less than 80% of the baseline reading is detected, will have Ang II initiated at 2 ng/kg/min through a peripheral IV. The infusion will be increased at the discretion of the clinical team based on the response of the patient until a SBP within 5% of the baseline SBP.<br>* Other names: Giapreza;|
| Experimental: Other Classes of Antihypertensive Agents<br>Participants taking any other class of Antihypertensive Agents will be placed into this group. Intervention: Drug: Angiotensin II. | Drug: Angiotensin II<br>* Participants in the ACE inhibitors, ARBs, and Other Classes of Antihypertensive Agents who's systolic blood pressure (SBP) is less than 80% of the baseline reading is detected, will have Ang II initiated at 2 ng/kg/min through a peripheral IV. The infusion will be increased at the discretion of the clinical team based on the response of the patient until a SBP within 5% of the baseline SBP.<br>* Other names: Giapreza;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean dose required to increase the SBP | The mean dose required to increase the SBP in these 3 cohorts with essential hypertension (ACE inhibitor, ARB, or those on another class of hypertensive agents) to within 5% of baseline or higher will be calculated. | up to 1 hour | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean value of Bradykinin | Mean values of Bradykinin 1-8 and Bradykinin 1-7 will be calculated and reported. | up to 1 hour | 
| Mean value of Angiontensin | Mean values of Angiotensin I, Angiotensin II, Angiotensin IV, Angiotensin 1-7, Angiotensin 1-5, Angiotensin 1-9, Angiotensin 2-10, Angiotensin 2-7, and Angiotensin 3-7 will be calculated and reported. | up to 1 hour | 
| Mean value of Aldosterone | Mean value of Aldosterone will be calculated and reported. | up to 1 hour | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Angiotensin II, Angiotensin Converting Enzyme Inhibitors, Angiotensin Receptor Blockers, Anesthesia-Mediated Hypotension