Hypotension, Anesthesia
Conditions
Keywords
ACEI, ARB, Hypotension, General Anesthesia, Methohexital, Propofol
Brief summary
Patient undergoing general anesthesia in elective surgery will be assigned to receive either methohexital or propofol general anesthesia. Hypotensive events during the first 15 minutes of induction will be compared between the groups to ascertain which drug is less likely to cause a hypotensive event.
Detailed description
Patients taking angiotensin converting-enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) are susceptible to hypotensive events during general anesthesia. The purpose of this study is to determine if the use of either methohexital or propofol general anesthesias is more likely to result in hypotensive events in these patients during their induction. Hemodynamic metrics like blood pressure, mean arterial pressure, and heart rate will be monitored during the induction process, under both drugs, for use as the main metrics, as well as the need for vasopressors in response to patient hypotension.
Interventions
DRUGMethohexital
Both drugs of interest are standard of care for use as general anesthetics. The purpose of the study is the determine the susceptibility of both drugs to inducing a hypotensive event.
DRUGPropofol
Both drugs of interest are standard of care for use as general anesthetics. The purpose of the study is the determine the susceptibility of both drugs to inducing a hypotensive event.
Sponsors
Milton S. Hershey Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* treated for at least 6 weeks with ACEIs or ARB * undergoing elective surgery under general endotracheal anesthesia * ASA Physical Class I or II
Exclusion criteria
* BMI \>45kg/m\^2 * taking both ACEI and ARB * history of difficult intubation in the past * require rapid sequence induction and intubation * uncontrolled baseline blood pressure (SBP\>180mmHg or DBP \>110 mmHg) at anesthesia preoperative clinic visit * contraindication to the use of propofol or methohexital * significant coronary artery disease * history of systolic heart failure * history of renal failure (creatine level \>2 mg/dL)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Had Hypotensive Events | Hemodynamic measurements will be taken during the first 15 minutes of anesthetic induction | Hypotensive events under either methohexital or propofol general anesthesia will be counted as the primary outcome measure |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Each Hypotension Episode | Hemodynamic measurements will be taken during the first 15 minutes of anesthetic induction | This is the length of time that systolic blood pressure was either: (1) \< 85 mmHg, or (2) a decrease of more than 30% from the individual's baseline SBP. |
| Systolic Blood Pressure | Hemodynamic measurements will be taken during the first 15 minutes of anesthetic induction | Systolic blood pressure will be measured through standard monitoring. |
| Diastolic Blood Pressure | Hemodynamic measurements will be taken during the first 15 minutes of anesthetic induction | Diastolic blood pressure will be measured through standard monitoring. |
| Heart Rate | Hemodynamic measurements will be taken during the first 15 minutes of anesthetic induction | Heart rate will be measured through standard monitoring. |
| Number of Participants With Refractory Hypotension | Hemodynamic measurements will be taken during the first 15 minutes of anesthetic induction | Refractory hypotension is defined as a hypotensive event that continues after 3 doses of vasopressors |
| Blood Levels of Epinephrine (at Baseline (Time 0) and 3,5,10 and 15 Min After Induction of Anesthesia) | Time 0,3,5,10 and 15 min following anesthetic induction | Serum concentrations of Epinephrine at predetermined time points (Baseline (Time 0) and 3,5,10 and 15 min) following anesthetic induction |
| Blood Levels of Angiotensin II (AII) (at Baseline (Time 0) and 3,5,10 and 15 Min After Anesthetic Induction) | Time 0,3,5,10 and 15 min following anesthetic induction | Serum concentrations of Angiotension II at predetermined time points (Baseline (Time 0) and 3,5,10 and 15 min) following anesthetic induction |
| Blood Levels of Arginine Vasopressin (AVP) (at Baseline (Time 0) and 3,5,10 and 15 Min After Anesthetic Induction) for Participants Who Did Not Receive AVP for Refractory Hypotension | Time 0,3,5,10 and 15 min following anesthetic induction | Serum concentrations of AVP at predetermined time points (Baseline (Time 0) and 3,5,10 and 15 min) following anesthetic induction determined for participants who did not receive AVP for refractory hypotension |
| Blood Levels of AVP (at Baseline (Time 0) and 3,5,10 and 15 Min) for Participants Who Received AVP for Refractory Hypotension | Time 0,3,5,10 and 15 min following anesthetic induction | Serum concentrations of AVP at predetermined time points (Baseline (Time 0) and 3,5,10 and 15 min), following anesthetic induction, determined for Participants who did not receive AVP for refractory hypotension |
| Serum Concentration of Norepinephrine (NE) (at Baseline (Time 0) and 3,5,10 and 15 Min After Anesthetic Induction) | Time 0,3,5,10 and 15 min following anesthetic induction | Serum concentrations of NE at predetermined time points (Baseline (Time 0) and 3,5,10 and 15 min) following anesthetic induction |
Countries
United States
Participant flow
Recruitment details
Recruitment was from 08/2016 through 08/2017 at the pre-anesthesia clinic and on the day of surgery in the pre-operative area.
Participants by arm
| Arm | Count |
|---|---|
| Methohexital Methohexital will be administered intravenously as a general anesthetic at a dosage of 1.5mg per kg of patient body weight.
Methohexital: Both drugs of interest are standard of care for use as general anesthetics. The purpose of the study is the determine the susceptibility of both drugs to inducing a hypotensive event. | 20 |
| Propofol Propofol will be administered intravenously as a general anesthetic at a dosage of 2.5mg per kg of patient body weight.
Propofol: Both drugs of interest are standard of care for use as general anesthetics. The purpose of the study is the determine the susceptibility of both drugs to inducing a hypotensive event. | 25 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 4 | 0 |
| Overall Study | Protocol Violation | 2 | 0 |
Baseline characteristics
| Characteristic | Methohexital | Propofol | Total |
|---|---|---|---|
| Age, Continuous | 64 years STANDARD_DEVIATION 9 | 60 years STANDARD_DEVIATION 14 | 61.9 years STANDARD_DEVIATION 11.8 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 7 Participants | 11 Participants | 18 Participants |
| Sex: Female, Male Male | 13 Participants | 14 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 0 / 20 |
| other Total, other adverse events | 0 / 25 | 0 / 20 |
| serious Total, serious adverse events | 0 / 25 | 0 / 20 |
Outcome results
Primary
Number of Participants Who Had Hypotensive Events
Hypotensive events under either methohexital or propofol general anesthesia will be counted as the primary outcome measure
Time frame: Hemodynamic measurements will be taken during the first 15 minutes of anesthetic induction
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Methohexital | Number of Participants Who Had Hypotensive Events | 8 Participants |
| Propofol | Number of Participants Who Had Hypotensive Events | 21 Participants |
p-value: 0.01log-binomial regression
Secondary
Blood Levels of Angiotensin II (AII) (at Baseline (Time 0) and 3,5,10 and 15 Min After Anesthetic Induction)
Serum concentrations of Angiotension II at predetermined time points (Baseline (Time 0) and 3,5,10 and 15 min) following anesthetic induction
Time frame: Time 0,3,5,10 and 15 min following anesthetic induction
Population: Blood samples were not available for some participants at some time points
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Methohexital | Blood Levels of Angiotensin II (AII) (at Baseline (Time 0) and 3,5,10 and 15 Min After Anesthetic Induction) | 3 min | 19.07 pg/ml | Standard Deviation 18.96 |
| Methohexital | Blood Levels of Angiotensin II (AII) (at Baseline (Time 0) and 3,5,10 and 15 Min After Anesthetic Induction) | 10 min | 24.46 pg/ml | Standard Deviation 17.91 |
| Methohexital | Blood Levels of Angiotensin II (AII) (at Baseline (Time 0) and 3,5,10 and 15 Min After Anesthetic Induction) | 5 min | 21.42 pg/ml | Standard Deviation 18.7 |
| Methohexital | Blood Levels of Angiotensin II (AII) (at Baseline (Time 0) and 3,5,10 and 15 Min After Anesthetic Induction) | 15 min | 22.16 pg/ml | Standard Deviation 18.46 |
| Methohexital | Blood Levels of Angiotensin II (AII) (at Baseline (Time 0) and 3,5,10 and 15 Min After Anesthetic Induction) | Time 0 | 21.71 pg/ml | Standard Deviation 17.17 |
| Propofol | Blood Levels of Angiotensin II (AII) (at Baseline (Time 0) and 3,5,10 and 15 Min After Anesthetic Induction) | 15 min | 17.63 pg/ml | Standard Deviation 16.42 |
| Propofol | Blood Levels of Angiotensin II (AII) (at Baseline (Time 0) and 3,5,10 and 15 Min After Anesthetic Induction) | Time 0 | 18.85 pg/ml | Standard Deviation 16.15 |
| Propofol | Blood Levels of Angiotensin II (AII) (at Baseline (Time 0) and 3,5,10 and 15 Min After Anesthetic Induction) | 3 min | 19.56 pg/ml | Standard Deviation 16.84 |
| Propofol | Blood Levels of Angiotensin II (AII) (at Baseline (Time 0) and 3,5,10 and 15 Min After Anesthetic Induction) | 5 min | 20.62 pg/ml | Standard Deviation 15.54 |
| Propofol | Blood Levels of Angiotensin II (AII) (at Baseline (Time 0) and 3,5,10 and 15 Min After Anesthetic Induction) | 10 min | 20.32 pg/ml | Standard Deviation 16.87 |
Secondary
Blood Levels of Arginine Vasopressin (AVP) (at Baseline (Time 0) and 3,5,10 and 15 Min After Anesthetic Induction) for Participants Who Did Not Receive AVP for Refractory Hypotension
Serum concentrations of AVP at predetermined time points (Baseline (Time 0) and 3,5,10 and 15 min) following anesthetic induction determined for participants who did not receive AVP for refractory hypotension
Time frame: Time 0,3,5,10 and 15 min following anesthetic induction
Population: Blood samples were not available for some participants at some time points
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Methohexital | Blood Levels of Arginine Vasopressin (AVP) (at Baseline (Time 0) and 3,5,10 and 15 Min After Anesthetic Induction) for Participants Who Did Not Receive AVP for Refractory Hypotension | 3 min | 25.07 pg/ml | Standard Deviation 17.41 |
| Methohexital | Blood Levels of Arginine Vasopressin (AVP) (at Baseline (Time 0) and 3,5,10 and 15 Min After Anesthetic Induction) for Participants Who Did Not Receive AVP for Refractory Hypotension | 10 min | 29.36 pg/ml | Standard Deviation 18.28 |
| Methohexital | Blood Levels of Arginine Vasopressin (AVP) (at Baseline (Time 0) and 3,5,10 and 15 Min After Anesthetic Induction) for Participants Who Did Not Receive AVP for Refractory Hypotension | 5 min | 34.66 pg/ml | Standard Deviation 19.12 |
| Methohexital | Blood Levels of Arginine Vasopressin (AVP) (at Baseline (Time 0) and 3,5,10 and 15 Min After Anesthetic Induction) for Participants Who Did Not Receive AVP for Refractory Hypotension | 15 min | 26.76 pg/ml | Standard Deviation 15 |
| Methohexital | Blood Levels of Arginine Vasopressin (AVP) (at Baseline (Time 0) and 3,5,10 and 15 Min After Anesthetic Induction) for Participants Who Did Not Receive AVP for Refractory Hypotension | Time 0 | 30.75 pg/ml | Standard Deviation 15.13 |
| Propofol | Blood Levels of Arginine Vasopressin (AVP) (at Baseline (Time 0) and 3,5,10 and 15 Min After Anesthetic Induction) for Participants Who Did Not Receive AVP for Refractory Hypotension | 15 min | 22.15 pg/ml | Standard Deviation 7.72 |
| Propofol | Blood Levels of Arginine Vasopressin (AVP) (at Baseline (Time 0) and 3,5,10 and 15 Min After Anesthetic Induction) for Participants Who Did Not Receive AVP for Refractory Hypotension | Time 0 | 29.76 pg/ml | Standard Deviation 16.17 |
| Propofol | Blood Levels of Arginine Vasopressin (AVP) (at Baseline (Time 0) and 3,5,10 and 15 Min After Anesthetic Induction) for Participants Who Did Not Receive AVP for Refractory Hypotension | 3 min | 26.50 pg/ml | Standard Deviation 16.34 |
| Propofol | Blood Levels of Arginine Vasopressin (AVP) (at Baseline (Time 0) and 3,5,10 and 15 Min After Anesthetic Induction) for Participants Who Did Not Receive AVP for Refractory Hypotension | 5 min | 23.99 pg/ml | Standard Deviation 13.71 |
| Propofol | Blood Levels of Arginine Vasopressin (AVP) (at Baseline (Time 0) and 3,5,10 and 15 Min After Anesthetic Induction) for Participants Who Did Not Receive AVP for Refractory Hypotension | 10 min | 16.37 pg/ml | Standard Deviation 9.18 |
Secondary
Blood Levels of AVP (at Baseline (Time 0) and 3,5,10 and 15 Min) for Participants Who Received AVP for Refractory Hypotension
Serum concentrations of AVP at predetermined time points (Baseline (Time 0) and 3,5,10 and 15 min), following anesthetic induction, determined for Participants who did not receive AVP for refractory hypotension
Time frame: Time 0,3,5,10 and 15 min following anesthetic induction
Population: Blood samples were not available for some participants at some time points
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Methohexital | Blood Levels of AVP (at Baseline (Time 0) and 3,5,10 and 15 Min) for Participants Who Received AVP for Refractory Hypotension | 3 min | 10.57 pg/ml | — |
| Methohexital | Blood Levels of AVP (at Baseline (Time 0) and 3,5,10 and 15 Min) for Participants Who Received AVP for Refractory Hypotension | 10 min | 13.93 pg/ml | Standard Deviation 8.93 |
| Methohexital | Blood Levels of AVP (at Baseline (Time 0) and 3,5,10 and 15 Min) for Participants Who Received AVP for Refractory Hypotension | 5 min | 13.73 pg/ml | Standard Deviation 9.83 |
| Methohexital | Blood Levels of AVP (at Baseline (Time 0) and 3,5,10 and 15 Min) for Participants Who Received AVP for Refractory Hypotension | 15 min | 12.85 pg/ml | Standard Deviation 1.22 |
| Methohexital | Blood Levels of AVP (at Baseline (Time 0) and 3,5,10 and 15 Min) for Participants Who Received AVP for Refractory Hypotension | Time 0 | 14.85 pg/ml | Standard Deviation 7.74 |
| Propofol | Blood Levels of AVP (at Baseline (Time 0) and 3,5,10 and 15 Min) for Participants Who Received AVP for Refractory Hypotension | 15 min | 63.86 pg/ml | Standard Deviation 45.64 |
| Propofol | Blood Levels of AVP (at Baseline (Time 0) and 3,5,10 and 15 Min) for Participants Who Received AVP for Refractory Hypotension | Time 0 | 33.28 pg/ml | Standard Deviation 28.96 |
| Propofol | Blood Levels of AVP (at Baseline (Time 0) and 3,5,10 and 15 Min) for Participants Who Received AVP for Refractory Hypotension | 3 min | 30.24 pg/ml | Standard Deviation 25.13 |
| Propofol | Blood Levels of AVP (at Baseline (Time 0) and 3,5,10 and 15 Min) for Participants Who Received AVP for Refractory Hypotension | 5 min | 29.89 pg/ml | Standard Deviation 21.28 |
| Propofol | Blood Levels of AVP (at Baseline (Time 0) and 3,5,10 and 15 Min) for Participants Who Received AVP for Refractory Hypotension | 10 min | 22.61 pg/ml | Standard Deviation 12.25 |
Secondary
Blood Levels of Epinephrine (at Baseline (Time 0) and 3,5,10 and 15 Min After Induction of Anesthesia)
Serum concentrations of Epinephrine at predetermined time points (Baseline (Time 0) and 3,5,10 and 15 min) following anesthetic induction
Time frame: Time 0,3,5,10 and 15 min following anesthetic induction
Population: Blood Samples were not available for some participants at some time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Methohexital | Blood Levels of Epinephrine (at Baseline (Time 0) and 3,5,10 and 15 Min After Induction of Anesthesia) | 3 min | 60.86 pg/ml | Standard Deviation 63.46 |
| Methohexital | Blood Levels of Epinephrine (at Baseline (Time 0) and 3,5,10 and 15 Min After Induction of Anesthesia) | 10 min | 40.96 pg/ml | Standard Deviation 36.97 |
| Methohexital | Blood Levels of Epinephrine (at Baseline (Time 0) and 3,5,10 and 15 Min After Induction of Anesthesia) | 5 min | 89.85 pg/ml | Standard Deviation 63.52 |
| Methohexital | Blood Levels of Epinephrine (at Baseline (Time 0) and 3,5,10 and 15 Min After Induction of Anesthesia) | 15 min | 46.28 pg/ml | Standard Deviation 35.17 |
| Methohexital | Blood Levels of Epinephrine (at Baseline (Time 0) and 3,5,10 and 15 Min After Induction of Anesthesia) | Time 0 | 70.89 pg/ml | Standard Deviation 52.57 |
| Propofol | Blood Levels of Epinephrine (at Baseline (Time 0) and 3,5,10 and 15 Min After Induction of Anesthesia) | 15 min | 39.56 pg/ml | Standard Deviation 27.77 |
| Propofol | Blood Levels of Epinephrine (at Baseline (Time 0) and 3,5,10 and 15 Min After Induction of Anesthesia) | Time 0 | 66.46 pg/ml | Standard Deviation 40.82 |
| Propofol | Blood Levels of Epinephrine (at Baseline (Time 0) and 3,5,10 and 15 Min After Induction of Anesthesia) | 3 min | 49.87 pg/ml | Standard Deviation 34.48 |
| Propofol | Blood Levels of Epinephrine (at Baseline (Time 0) and 3,5,10 and 15 Min After Induction of Anesthesia) | 5 min | 57.29 pg/ml | Standard Deviation 31.95 |
| Propofol | Blood Levels of Epinephrine (at Baseline (Time 0) and 3,5,10 and 15 Min After Induction of Anesthesia) | 10 min | 44.17 pg/ml | Standard Deviation 29.95 |
Secondary
Diastolic Blood Pressure
Diastolic blood pressure will be measured through standard monitoring.
Time frame: Hemodynamic measurements will be taken during the first 15 minutes of anesthetic induction
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Methohexital | Diastolic Blood Pressure | 85 mm Hg | Standard Deviation 12 |
| Propofol | Diastolic Blood Pressure | 72 mm Hg | Standard Deviation 11 |
Secondary
Duration of Each Hypotension Episode
This is the length of time that systolic blood pressure was either: (1) \< 85 mmHg, or (2) a decrease of more than 30% from the individual's baseline SBP.
Time frame: Hemodynamic measurements will be taken during the first 15 minutes of anesthetic induction
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Methohexital | Duration of Each Hypotension Episode | 5.1 min | Standard Deviation 3.7 |
| Propofol | Duration of Each Hypotension Episode | 4.8 min | Standard Deviation 3.4 |
Secondary
Heart Rate
Heart rate will be measured through standard monitoring.
Time frame: Hemodynamic measurements will be taken during the first 15 minutes of anesthetic induction
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Methohexital | Heart Rate | 80 bpm | Standard Deviation 14 |
| Propofol | Heart Rate | 76 bpm | Standard Deviation 15 |
Secondary
Number of Participants With Refractory Hypotension
Refractory hypotension is defined as a hypotensive event that continues after 3 doses of vasopressors
Time frame: Hemodynamic measurements will be taken during the first 15 minutes of anesthetic induction
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Methohexital | Number of Participants With Refractory Hypotension | 2 Participants |
| Propofol | Number of Participants With Refractory Hypotension | 5 Participants |
p-value: 0.37log binomial regression
Secondary
Serum Concentration of Norepinephrine (NE) (at Baseline (Time 0) and 3,5,10 and 15 Min After Anesthetic Induction)
Serum concentrations of NE at predetermined time points (Baseline (Time 0) and 3,5,10 and 15 min) following anesthetic induction
Time frame: Time 0,3,5,10 and 15 min following anesthetic induction
Population: Blood samples were not available for some participants at some time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Methohexital | Serum Concentration of Norepinephrine (NE) (at Baseline (Time 0) and 3,5,10 and 15 Min After Anesthetic Induction) | 3 min | 175.24 pg/ml | Standard Deviation 204.52 |
| Methohexital | Serum Concentration of Norepinephrine (NE) (at Baseline (Time 0) and 3,5,10 and 15 Min After Anesthetic Induction) | 10 min | 179.42 pg/ml | Standard Deviation 243.88 |
| Methohexital | Serum Concentration of Norepinephrine (NE) (at Baseline (Time 0) and 3,5,10 and 15 Min After Anesthetic Induction) | 5 min | 212.34 pg/ml | Standard Deviation 230.44 |
| Methohexital | Serum Concentration of Norepinephrine (NE) (at Baseline (Time 0) and 3,5,10 and 15 Min After Anesthetic Induction) | 15 min | 173.25 pg/ml | Standard Deviation 221.62 |
| Methohexital | Serum Concentration of Norepinephrine (NE) (at Baseline (Time 0) and 3,5,10 and 15 Min After Anesthetic Induction) | Time 0 | 205.68 pg/ml | Standard Deviation 231.37 |
| Propofol | Serum Concentration of Norepinephrine (NE) (at Baseline (Time 0) and 3,5,10 and 15 Min After Anesthetic Induction) | 15 min | 147.32 pg/ml | Standard Deviation 163.66 |
| Propofol | Serum Concentration of Norepinephrine (NE) (at Baseline (Time 0) and 3,5,10 and 15 Min After Anesthetic Induction) | Time 0 | 200.59 pg/ml | Standard Deviation 238.26 |
| Propofol | Serum Concentration of Norepinephrine (NE) (at Baseline (Time 0) and 3,5,10 and 15 Min After Anesthetic Induction) | 3 min | 166.04 pg/ml | Standard Deviation 222.77 |
| Propofol | Serum Concentration of Norepinephrine (NE) (at Baseline (Time 0) and 3,5,10 and 15 Min After Anesthetic Induction) | 5 min | 208.93 pg/ml | Standard Deviation 214.2 |
| Propofol | Serum Concentration of Norepinephrine (NE) (at Baseline (Time 0) and 3,5,10 and 15 Min After Anesthetic Induction) | 10 min | 168.39 pg/ml | Standard Deviation 185.79 |
p-value: 0.277Ratio of Geometric Means
Secondary
Systolic Blood Pressure
Systolic blood pressure will be measured through standard monitoring.
Time frame: Hemodynamic measurements will be taken during the first 15 minutes of anesthetic induction
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Methohexital | Systolic Blood Pressure | 141 mm Hg | Standard Deviation 26 |
| Propofol | Systolic Blood Pressure | 126 mm Hg | Standard Deviation 22 |