Cardiac Disease
Conditions
Brief summary
The relative increase in the mPAP with the same unit increase in MAP adjusted for baseline, and RV function assessed by GLS, between VP and NE in patients with normal and increased pulmonary artery pressure, who require vasopressor support during cardiac surgery.
Detailed description
The specific aims of our study are to compare 1) the relative increase in the mPAP with the same unit increase in MAP adjusted for baseline and 2) RV function assessed by GLS, between VP and NE in patients with normal and increased pulmonary artery pressure, who require vasopressor support during cardiac surgery. We hypothesize that the use of vasopressin compared with norepinephrine induces a lower mPAP-to-MAP ratio, in cardiac surgical patients with and without pulmonary hypertension who require intraoperative vasopressor support. Second, we will test the hypothesis that vasopressin is associated with improved right ventricular global longitudinal strain compared to norepinephrine in patients requiring vasopressor support during cardiac surgery.
Interventions
DRUGVasopressin
Vasopressin (20 IU/100 ml in 5% dextrose) were stored in pre-mixed bags in the operating room, readily available for continuous infusion administration via pre-programed infusion pumps
DRUGNorepinephrine
Norepinephrine (4 mg/250ml in 5% dextrose) were stored in pre-mixed bags in the operating room, readily available for continuous infusion administration via pre-programed infusion pumps
Sponsors
The Cleveland Clinic
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Randomized cluster crossover study
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Adults\> 18 years of age * Elective cardiac surgery with the use of CPB * Patients with pulmonary artery catheter insertion * Systemic hypotension (MAP \< 70 mmHg) requiring continuous infusion of vasopressor
Exclusion criteria
* Transplant surgery * Ventricular assist device implantation other than intra-aortic balloon counter-pulsation * Pulmonary endarterectomy * Thoracoabdominal aneurysm repair * Inhalational pulmonary vasodilators (e.g. Epoprostenol) administration before insertion of pulmonary artery catheter * Vasopressin is started as the first choice of pressor per clinical staff discretion
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| mPAP-to-MAP Ratio | during 20 minute period after chest closure | The intraoperative mean pulmonary artery pressure(mPAP) adjusted for systemic mean arterial pressure(MAP), using a time-weighted average mPAP-to-MAP ratio measured during 20 minute period after chest closure |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| RV Free Wall Strain | during 20 minutes period after chest closure | Right Ventricular Free Wall Longitudinal Strain (RV FWLS) is a measure of the deformation (strain) of the right ventricle's free wall (the part not attached to the septum) during contraction. It quantifies how much the myocardium in the free wall of the right ventricle shortens along its longitudinal axis (base to apex) during systole (contraction). It is expressed as a negative percentage (%), where more negative values indicate better contractility (e.g., -20% is better than -10%). In this study, it was measured by transesophageal echocardiography in the 2D mid-esophageal four-chamber view during a steady state period after chest closure |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORMariya Geube, MD
The Cleveland Clinic
Participant flow
Pre-assignment details
This is a unblinded alternating trial. The treatment will be randomized in one week blocks and not by patient, using the RedCap system. This means that during any week, eligible patients will be exposed to the same vasopressor agent (vasopressin or norepinephrine). And the following week there will be new randomization in place. Allocations will be directly communicated to anesthesia personnel and by signs prominently displayed in anesthesia ready room.
Participants by arm
| Arm | Count |
|---|---|
| Patients Using Intraoperative Vasopressin Hemodynamic effect of vasopressin on the pulmonary circulation in cardiac surgery patients | 70 |
| Patients Using Intraoperative Norepinephrine Hemodynamic effect of Norepinephrine on the pulmonary circulation in cardiac surgery patients | 83 |
| Total | 153 |
Baseline characteristics
| Characteristic | Patients Using Intraoperative Vasopressin | Total | Patients Using Intraoperative Norepinephrine |
|---|---|---|---|
| Age, Continuous | 66 years STANDARD_DEVIATION 12 | 66 years STANDARD_DEVIATION 13 | 66 years STANDARD_DEVIATION 13 |
| BMI | 29 kg/m^2 STANDARD_DEVIATION 6 | 28.5 kg/m^2 STANDARD_DEVIATION 6.5 | 28.2 kg/m^2 STANDARD_DEVIATION 6.5 |
| Comorbid conditions Cerebral vascular disease | 12 Participants | 36 Participants | 24 Participants |
| Comorbid conditions Chronic kidney disease | 2 Participants | 9 Participants | 7 Participants |
| Comorbid conditions Congestive heart failure | 30 Participants | 69 Participants | 39 Participants |
| Comorbid conditions Coronary artery disease | 49 Participants | 110 Participants | 61 Participants |
| Comorbid conditions Diabetes | 21 Participants | 50 Participants | 29 Participants |
| Comorbid conditions Hyperlipidemia | 42 Participants | 93 Participants | 51 Participants |
| Comorbid conditions Hypertension | 53 Participants | 119 Participants | 66 Participants |
| Comorbid conditions Peripheral artery disease | 9 Participants | 26 Participants | 17 Participants |
| Comorbid conditions Pulmonary hypertension | 19 Participants | 40 Participants | 21 Participants |
| Comorbid conditions Smoking history | 34 Participants | 77 Participants | 43 Participants |
| Preoperative RV dysfunction Mild | 14 Participants | 28 Participants | 14 Participants |
| Preoperative RV dysfunction Moderate or severe | 6 Participants | 12 Participants | 6 Participants |
| Preoperative RV dysfunction Normal | 50 Participants | 113 Participants | 63 Participants |
| Primary or repeat surgery Primary surgery | 38 Participants | 88 Participants | 50 Participants |
| Primary or repeat surgery Reoperative surgery | 32 Participants | 65 Participants | 33 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 70 Participants | 153 Participants | 83 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 18 Participants | 50 Participants | 32 Participants |
| Sex: Female, Male Male | 52 Participants | 103 Participants | 51 Participants |
| Surgery type Aortic surgery | 7 Participants | 12 Participants | 5 Participants |
| Surgery type Aortic valve surgery | 13 Participants | 21 Participants | 8 Participants |
| Surgery type CABG + aortic valve surgery | 9 Participants | 16 Participants | 7 Participants |
| Surgery type CABG + mitral valve surgery | 3 Participants | 7 Participants | 4 Participants |
| Surgery type Isolated CABG | 10 Participants | 25 Participants | 15 Participants |
| Surgery type Mitral valve surgery | 4 Participants | 12 Participants | 8 Participants |
| Surgery type Multi-valve procedures | 18 Participants | 51 Participants | 33 Participants |
| Surgery type Other | 6 Participants | 9 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
mPAP-to-MAP Ratio
The intraoperative mean pulmonary artery pressure(mPAP) adjusted for systemic mean arterial pressure(MAP), using a time-weighted average mPAP-to-MAP ratio measured during 20 minute period after chest closure
Time frame: during 20 minute period after chest closure
Population: Not all the patients in the 2 groups with preoperative pulmonary arterial hypertension, we only included the eligible patients.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| The Use of Vasopressin | mPAP-to-MAP Ratio | mPAP-to-MAP ratio | 0.394 ratio of mPAP-to-MAP | Standard Deviation 0.086 |
| The Use of Vasopressin | mPAP-to-MAP Ratio | mPAP-to-MAP ratio with preop pulmonary hypertension | 0.42 ratio of mPAP-to-MAP | Standard Deviation 0.082 |
| The Use of Vasopressin | mPAP-to-MAP Ratio | mPAP-to-MAP ratio without preop pulmonary hypertension | 0.37 ratio of mPAP-to-MAP | Standard Deviation 0.084 |
| The Use of Norepinephrine | mPAP-to-MAP Ratio | mPAP-to-MAP ratio | 0.385 ratio of mPAP-to-MAP | Standard Deviation 0.094 |
| The Use of Norepinephrine | mPAP-to-MAP Ratio | mPAP-to-MAP ratio with preop pulmonary hypertension | 0.40 ratio of mPAP-to-MAP | Standard Deviation 0.093 |
| The Use of Norepinephrine | mPAP-to-MAP Ratio | mPAP-to-MAP ratio without preop pulmonary hypertension | 0.36 ratio of mPAP-to-MAP | Standard Deviation 0.092 |
p-value: 0.5395% CI: [-0.043, 0.022]Mixed Models Analysis
Comparison: mPAP-to-MAP ratio was compared between patients with pre-existing pulmonary hypertension of use of vasopressin and norepinephrine. Preoperative pulmonary arterial hypertension was defined by using the cut-off value of 25 mmHg for the time-weighted average mPAP, i.e., time weighted average mPAP \< 25 mmHg indicated absence of preoperative pulmonary arterial hypertension; otherwise, presence of preoperative pulmonary hypertension.p-value: 0.2695% CI: [-0.061, 0.016]Mixed Models Analysis
Comparison: mPAP-to-MAP ratio was compared between patients without pre-existing pulmonary hypertension of use of vasopressin and norepinephrine. Preoperative pulmonary arterial hypertension was defined by using the cut-off value of 25 mmHg for the time-weighted average mPAP, i.e., time weighted average mPAP \< 25 mmHg indicated absence of preoperative pulmonary arterial hypertension; otherwise, presence of preoperative pulmonary hypertension.p-value: 0.8895% CI: [-0.05, 0.043]Mixed Models Analysis
Secondary
RV Free Wall Strain
Right Ventricular Free Wall Longitudinal Strain (RV FWLS) is a measure of the deformation (strain) of the right ventricle's free wall (the part not attached to the septum) during contraction. It quantifies how much the myocardium in the free wall of the right ventricle shortens along its longitudinal axis (base to apex) during systole (contraction). It is expressed as a negative percentage (%), where more negative values indicate better contractility (e.g., -20% is better than -10%). In this study, it was measured by transesophageal echocardiography in the 2D mid-esophageal four-chamber view during a steady state period after chest closure
Time frame: during 20 minutes period after chest closure
Population: Included all patients for RV free wall strain. As not all the patients with/without preoperative pulmonary arterial hypertension, so the study pop in subgroup are different.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| The Use of Vasopressin | RV Free Wall Strain | RV free wall strain | -18.2 percentage of RV free wall strain | Standard Deviation 8.4 |
| The Use of Vasopressin | RV Free Wall Strain | RV free wall strain with preop pulmonary hypertension | -17.5 percentage of RV free wall strain | Standard Deviation 8.4 |
| The Use of Vasopressin | RV Free Wall Strain | RV free wall strain without preop pulmonary hypertension | -19.2 percentage of RV free wall strain | Standard Deviation 8.4 |
| The Use of Norepinephrine | RV Free Wall Strain | RV free wall strain | -19.4 percentage of RV free wall strain | Standard Deviation 7.2 |
| The Use of Norepinephrine | RV Free Wall Strain | RV free wall strain with preop pulmonary hypertension | -18.9 percentage of RV free wall strain | Standard Deviation 8.1 |
| The Use of Norepinephrine | RV Free Wall Strain | RV free wall strain without preop pulmonary hypertension | -20.0 percentage of RV free wall strain | Standard Deviation 5.7 |
p-value: 0.3795% CI: [-6, 2.3]Mixed Models Analysis
Comparison: RV free wall strain compare between patients with pre-existing pulmonary hypertension of use of vasopressin and norepinephrine. Preoperative pulmonary arterial hypertension was defined by using the cut-off value of 25 mmHg for the time-weighted average mPAP, i.e., time weighted average mPAP \< 25 mmHg indicated absence of preoperative pulmonary arterial hypertension; otherwise, presence of preoperative pulmonary hypertension;p-value: 0.3995% CI: [-7.1, 2.8]Mixed Models Analysis
Comparison: We examined the effect of norepinephrine versus vasopressin on right ventricular free wall strain by separately considering patients who did not have preoperative pulmonary hypertension.~Preoperative pulmonary arterial hypertension was defined by using the cut-off value of 25 mmHg for the time-weighted average mPAP, i.e., time weighted average mPAP \< 25 mmHg indicated absence of preoperative pulmonary arterial hypertension; otherwise, presence of preoperative pulmonary hypertension.p-value: 0.6395% CI: [-7.6, 4.6]Mixed Models Analysis