Hypertension
Conditions
Keywords
Angiotensin II, Angiotensin Converting Enzyme Inhibitors, Angiotensin Receptor Blockers, Anesthesia-Mediated Hypotension
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
Interventions
DRUGAngiotensin II
Participants in the ACE inhibitors, angiotensin-receptor blockers (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.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
National Institute on Aging (NIA)
Wake Forest University Health Sciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Median Dose Required to Increase the Systolic Blood Pressure (SBP) | up to 1 hour | The median 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Serum Level of Bradykinin 1-7 | Up to 1 hour | Median serum level of Bradykinin 1-7 |
| Median Serum Level of Bradykinin 1-5 | Up to 1 hour | Median serum level of Bradykinin 1-5 |
| Median Serum Level of Aldosterone | Up to 1 hour | Median serum level of Aldosterone |
| Median Serum Level of Angiotensin I | Up to 1 hour | Median serum level of Angiotensin I |
| Median Serum Level of Angiotensin II | up to 1 hour | Median serum level of Angiotensin II |
| Median Serum Level of Angiotensin IV | Up to 1 hour | Median serum level of Angiotensin IV |
| Median Serum Level of Bradykinin 1-8 | up to 1 hour | Median serum level of Bradykinin 1-8 |
| Median Serum Level of Angiotensin 1-5 | Up to 1 hour | Median serum level of Angiotensin 1-5 |
| Median Serum Level of Angiotensin 1-9 | Up to 1 hour | Median serum level of Angiotensin 1-9 |
| Median Serum Level of Angiotensin 2-10 | Up to 1 hour | Median serum level of Angiotensin 2-10 |
| Median Serum Level of Angiotensin 2-7 | Up to 1 hour | Median serum level of Angiotensin 2-7 |
| Median Serum Level of Angiotensin 3-7 | Up to 1 hour | Median serum level of Angiotensin 3-7 |
| Median Serum Level of Angiotensin 1-12 | Up to 1 hour | Median serum level of Angiotensin 1-12 |
| Median Serum Level of Angiotensin 1-7 | Up to 1 hour | Median serum level of Angiotensin 1-7 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Participants on ACE Inhibitors Participants taking ACE inhibitors (angiotensin-converting enzyme inhibitors)will be placed into this group. Intervention: Drug: Angiotensin II.
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. | 7 |
| Participants on ARBs Participants taking ARBs (angiotensin-receptor blockers) will be placed into this group. Intervention: Drug: Angiotensin II.
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. | 8 |
| Other Classes of Antihypertensive Agents Participants taking any other class of Antihypertensive Agents will be placed into this group. Intervention: Drug: Angiotensin II.
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. | 9 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | screenfail | 3 | 3 | 2 |
Baseline characteristics
| Characteristic | Participants on ACE Inhibitors | Participants on ARBs | Other Classes of Antihypertensive Agents | Total |
|---|---|---|---|---|
| Age, Continuous | 57.25 years STANDARD_DEVIATION 6.16 | 67.75 years STANDARD_DEVIATION 5.87 | 67.22 years STANDARD_DEVIATION 6.76 | 65.29 years STANDARD_DEVIATION 7.16 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 8 Participants | 9 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 6 Participants | 6 Participants | 7 Participants | 19 Participants |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 4 Participants | 11 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 5 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 8 | 0 / 7 |
| other Total, other adverse events | 1 / 5 | 2 / 8 | 0 / 7 |
| serious Total, serious adverse events | 0 / 5 | 0 / 8 | 0 / 7 |
Outcome results
Primary
Median Dose Required to Increase the Systolic Blood Pressure (SBP)
The median 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.
Time frame: up to 1 hour
Population: ACE Inhibitor Arm: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol ARB Arm: 2 patients did not reach the treatment goal in this group and were therefore excluded from primary outcome analysis Other Classes of Antihypertensive Agents Arm: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Participants on ACE Inhibitors | Median Dose Required to Increase the Systolic Blood Pressure (SBP) | 35 ng/kg/min |
| Participants on ARBs | Median Dose Required to Increase the Systolic Blood Pressure (SBP) | 43 ng/kg/min |
| Other Classes of Antihypertensive Agents | Median Dose Required to Increase the Systolic Blood Pressure (SBP) | 45 ng/kg/min |
Secondary
Median Serum Level of Aldosterone
Median serum level of Aldosterone
Time frame: Up to 1 hour
Population: ACE Inhibitor Arm: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol Other Classes of Antihypertensive Agents Arm: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Participants on ACE Inhibitors | Median Serum Level of Aldosterone | 293 pmol/L |
| Participants on ARBs | Median Serum Level of Aldosterone | 293 pmol/L |
| Other Classes of Antihypertensive Agents | Median Serum Level of Aldosterone | 230 pmol/L |
Secondary
Median Serum Level of Angiotensin 1-12
Median serum level of Angiotensin 1-12
Time frame: Up to 1 hour
Population: ACE Inhibitors Arm: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol, 2 patients unable to get sample.~ARBs Arm: 1 patient unable to get sample. Other Classes of Antihypertensive Agents: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol, 2 patients unable to get sample.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Participants on ACE Inhibitors | Median Serum Level of Angiotensin 1-12 | 940 pmol/L |
| Participants on ARBs | Median Serum Level of Angiotensin 1-12 | 1011 pmol/L |
| Other Classes of Antihypertensive Agents | Median Serum Level of Angiotensin 1-12 | 674 pmol/L |
Secondary
Median Serum Level of Angiotensin 1-5
Median serum level of Angiotensin 1-5
Time frame: Up to 1 hour
Population: ACE Inhibitors Arm: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol Other Classes of Antihypertensive Agents Arm: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Participants on ACE Inhibitors | Median Serum Level of Angiotensin 1-5 | 0 pmol/L |
| Participants on ARBs | Median Serum Level of Angiotensin 1-5 | 0 pmol/L |
| Other Classes of Antihypertensive Agents | Median Serum Level of Angiotensin 1-5 | 0 pmol/L |
Secondary
Median Serum Level of Angiotensin 1-7
Median serum level of Angiotensin 1-7
Time frame: Up to 1 hour
Population: ACE Inhibitors Arm: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol Other Classes of Antihypertensive Agents Arm: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Participants on ACE Inhibitors | Median Serum Level of Angiotensin 1-7 | 8.7 pmol/L |
| Participants on ARBs | Median Serum Level of Angiotensin 1-7 | 1.8 pmol/L |
| Other Classes of Antihypertensive Agents | Median Serum Level of Angiotensin 1-7 | 0 pmol/L |
Secondary
Median Serum Level of Angiotensin 1-9
Median serum level of Angiotensin 1-9
Time frame: Up to 1 hour
Population: ACE Inhibitors Arm: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol Other Classes of Antihypertensive Agents: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Participants on ACE Inhibitors | Median Serum Level of Angiotensin 1-9 | 0 pmol/L |
| Participants on ARBs | Median Serum Level of Angiotensin 1-9 | 0 pmol/L |
| Other Classes of Antihypertensive Agents | Median Serum Level of Angiotensin 1-9 | 0 pmol/L |
Secondary
Median Serum Level of Angiotensin 2-10
Median serum level of Angiotensin 2-10
Time frame: Up to 1 hour
Population: ACE Inhibitors Arm: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol Other Classes of Antihypertensive Agents Arm: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Participants on ACE Inhibitors | Median Serum Level of Angiotensin 2-10 | 0 pmol/L |
| Participants on ARBs | Median Serum Level of Angiotensin 2-10 | 0 pmol/L |
| Other Classes of Antihypertensive Agents | Median Serum Level of Angiotensin 2-10 | 0 pmol/L |
Secondary
Median Serum Level of Angiotensin 2-7
Median serum level of Angiotensin 2-7
Time frame: Up to 1 hour
Population: ACE Inhibitors Arm: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol Other Classes of Antihypertensive Agents: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Participants on ACE Inhibitors | Median Serum Level of Angiotensin 2-7 | 0 pmol/L |
| Participants on ARBs | Median Serum Level of Angiotensin 2-7 | 0 pmol/L |
| Other Classes of Antihypertensive Agents | Median Serum Level of Angiotensin 2-7 | 0 pmol/L |
Secondary
Median Serum Level of Angiotensin 3-7
Median serum level of Angiotensin 3-7
Time frame: Up to 1 hour
Population: ACE Inhibitors Arm: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol Other Classes of Antihypertensive Agents: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Participants on ACE Inhibitors | Median Serum Level of Angiotensin 3-7 | 0 pmol/L |
| Participants on ARBs | Median Serum Level of Angiotensin 3-7 | 0 pmol/L |
| Other Classes of Antihypertensive Agents | Median Serum Level of Angiotensin 3-7 | 0 pmol/L |
Secondary
Median Serum Level of Angiotensin I
Median serum level of Angiotensin I
Time frame: Up to 1 hour
Population: ACE Inhibitor Arm: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol Other Classes of Antihypertensive Agents Arm: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Participants on ACE Inhibitors | Median Serum Level of Angiotensin I | 8.7 pmol/L |
| Participants on ARBs | Median Serum Level of Angiotensin I | 1.8 pmol/L |
| Other Classes of Antihypertensive Agents | Median Serum Level of Angiotensin I | 0 pmol/L |
Secondary
Median Serum Level of Angiotensin II
Median serum level of Angiotensin II
Time frame: up to 1 hour
Population: ACE Inhibitors Arm: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol Other Classes of Antihypertensive Agents Arm: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Participants on ACE Inhibitors | Median Serum Level of Angiotensin II | 10.9 pmol/L |
| Participants on ARBs | Median Serum Level of Angiotensin II | 31.2 pmol/L |
| Other Classes of Antihypertensive Agents | Median Serum Level of Angiotensin II | 10.2 pmol/L |
Secondary
Median Serum Level of Angiotensin IV
Median serum level of Angiotensin IV
Time frame: Up to 1 hour
Population: ACE Inhibitors Arm: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol Other Classes of Antihypertensive Agents: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Participants on ACE Inhibitors | Median Serum Level of Angiotensin IV | 0 pmol/L |
| Participants on ARBs | Median Serum Level of Angiotensin IV | 1 pmol/L |
| Other Classes of Antihypertensive Agents | Median Serum Level of Angiotensin IV | 0 pmol/L |
Secondary
Median Serum Level of Bradykinin 1-5
Median serum level of Bradykinin 1-5
Time frame: Up to 1 hour
Population: ACE Inhibitor Arm: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol Other Classes of Antihypertensive Arm: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Participants on ACE Inhibitors | Median Serum Level of Bradykinin 1-5 | 2341 pmol/L |
| Participants on ARBs | Median Serum Level of Bradykinin 1-5 | 353 pmol/L |
| Other Classes of Antihypertensive Agents | Median Serum Level of Bradykinin 1-5 | 375 pmol/L |
Secondary
Median Serum Level of Bradykinin 1-7
Median serum level of Bradykinin 1-7
Time frame: Up to 1 hour
Population: ACE Inhibitor Arm: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol Other Classes of Antihypertensive Agents: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Participants on ACE Inhibitors | Median Serum Level of Bradykinin 1-7 | 24457 pmol/L |
| Participants on ARBs | Median Serum Level of Bradykinin 1-7 | 19335 pmol/L |
| Other Classes of Antihypertensive Agents | Median Serum Level of Bradykinin 1-7 | 17438 pmol/L |
Secondary
Median Serum Level of Bradykinin 1-8
Median serum level of Bradykinin 1-8
Time frame: up to 1 hour
Population: ACE Inhibitor Arm: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol Other Classes of Antihypertensive Agents Arm: 2 patients did not experience hypotension and therefore did not receive the Ang II per protocol
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Participants on ACE Inhibitors | Median Serum Level of Bradykinin 1-8 | 127043 pmol/L |
| Participants on ARBs | Median Serum Level of Bradykinin 1-8 | 105405 pmol/L |
| Other Classes of Antihypertensive Agents | Median Serum Level of Bradykinin 1-8 | 101169 pmol/L |