Angiotensin II in General Anesthesia

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

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.

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

Angiotensin II, Angiotensin Converting Enzyme Inhibitors, Angiotensin Receptor Blockers, Anesthesia-Mediated Hypotension

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

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

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

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.

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.

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.

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

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