Cardiovascular Shock, Circulatory Shock
Conditions
Brief summary
This is an open-label, single center, trial that will enroll up to 25 participants with circulatory shock after cardiac surgery. Participants will be administered a topical sublingual nitroglycerin solution and assessed for changes microcirculatory blood flow using incident dark field microscopy.
Interventions
Topical nitroglycerin solution
Sponsors
University of Pennsylvania
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Adult patients receiving elective CABG or valvular surgery requiring cardiopulmonary bypass * Receiving postoperative catecholamine therapy to maintain a MAP \> 65mmHg, cardiac index \> 2 despite initial fluid resuscitation * Invasive hemodynamic monitoring
Exclusion criteria
* Surgical hemorrhage * Unable to tolerate sublingual microcirculatory flow imaging * Known intolerance or allergy to nitroglycerin * Inadequate microcirculation imaging (based on Massey Score)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Perfused Vessel Density (PVD) | Preoperative Control Group: assessed once preoperatively. For the topical nitroglycerin group, PVD measurements were obtained after surgery (baseline), then 3-minutes and 30-minutes after topical nitroglycerin administration. | Estimate of functional capillary density. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Arterial Pressure | MAP was recorded for the control group, then for the NTG group at postoperative baseline, 3-minutes and 30-minutes after topical NTG application. | Mean arterial blood pressure |
| Cardiac Index | Cardiac output was measured for the control group, then for the NTG group at postoperative baseline, 3-minuts, and 30-minutes after topical NTG application | Cardiac output relative to patients body surface area |
| Central Venous Pressure | CVP was recorded for the control group, then for the NTG group at postoperative baseline, 3-minutes, and 30-minutes after topical NTG application | surrogate measure for right atrial pressure |
Countries
United States
Participant flow
Recruitment details
Patient recruitment completed between August 1 and October 30, 2021.
Pre-assignment details
20 patients were enrolled to obtain preoperative control microcirculation measurements only. 20 additional patients would be needed for the NTG challenge. NTG patients were enrolled prior to surgery, but not included if they did not meet postop inclusion criteria.
Participants by arm
| Arm | Count |
|---|---|
| Topical Nitroglycerin A topical nitroglycerin solution will be applied to the area of interest
Nitroglycerin Topical Product: Topical nitroglycerin solution | 20 |
| Preoperative Control Group 20 subjects planned for elective cardiovascular surgery were enrolled to measure baseline microvascular function by sublingual incident darkfield microscopy imaging. | 20 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Did not have functioning PA catheter | 1 | 0 |
| Overall Study | Did not require vasopressors | 1 | 0 |
| Overall Study | Inadequate video quality | 2 | 0 |
Baseline characteristics
| Characteristic | Topical Nitroglycerin | Preoperative Control Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 9 Participants | 11 Participants | 20 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants | 9 Participants | 20 Participants |
| Age, Continuous | 64 years STANDARD_DEVIATION 9 | 67 years STANDARD_DEVIATION 11 | 65 years STANDARD_DEVIATION 10 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants | 20 Participants | 38 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 3 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 18 Participants | 18 Participants | 36 Participants |
| Sex: Female, Male Female | 5 Participants | 5 Participants | 10 Participants |
| Sex: Female, Male Male | 15 Participants | 15 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 0 / 20 | 0 / 20 | 0 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 | 0 / 20 |
Outcome results
Primary
Perfused Vessel Density (PVD)
Estimate of functional capillary density.
Time frame: Preoperative Control Group: assessed once preoperatively. For the topical nitroglycerin group, PVD measurements were obtained after surgery (baseline), then 3-minutes and 30-minutes after topical nitroglycerin administration.
Population: Sublingual microcirculation measurements were obtained in a preoperative control group to serve as a healthy control measurement to compare against measurements in patients with shock. The preoperative control group only had one PVD measurement taken. Sublingual microcirculation measurements in the topical nitroglycerin group were measured after surgery (baseline), then 3-minutes and 30-minutes after NTG solution application.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Preoperative Control Group | Perfused Vessel Density (PVD) | 24.81 mm/mm^2 | Standard Deviation 3.51 |
| Topical Nitroglycerin Group Postop Baseline | Perfused Vessel Density (PVD) | 20.44 mm/mm^2 | Standard Deviation 3.38 |
| Topical Nitroglycerin Group 3-minutes Post-NTG | Perfused Vessel Density (PVD) | 26.41 mm/mm^2 | Standard Deviation 3.5 |
| Topical Nitroglycerin Group 30-minutes Post-NTG | Perfused Vessel Density (PVD) | 21.88 mm/mm^2 | Standard Deviation 3.84 |
Secondary
Cardiac Index
Cardiac output relative to patients body surface area
Time frame: Cardiac output was measured for the control group, then for the NTG group at postoperative baseline, 3-minuts, and 30-minutes after topical NTG application
Population: Same groups as the primary outcome
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Preoperative Control Group | Cardiac Index | 2.54 L/min/m^2 | Standard Deviation 0.79 |
| Topical Nitroglycerin Group Postop Baseline | Cardiac Index | 2.85 L/min/m^2 | Standard Deviation 0.81 |
| Topical Nitroglycerin Group 3-minutes Post-NTG | Cardiac Index | 2.88 L/min/m^2 | Standard Deviation 0.9 |
| Topical Nitroglycerin Group 30-minutes Post-NTG | Cardiac Index | 2.83 L/min/m^2 | Standard Deviation 0.76 |
Secondary
Central Venous Pressure
surrogate measure for right atrial pressure
Time frame: CVP was recorded for the control group, then for the NTG group at postoperative baseline, 3-minutes, and 30-minutes after topical NTG application
Population: Same as the primary outcome
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Preoperative Control Group | Central Venous Pressure | 16.7 mmHg | Standard Deviation 5.24 |
| Topical Nitroglycerin Group Postop Baseline | Central Venous Pressure | 9.35 mmHg | Standard Deviation 3.79 |
| Topical Nitroglycerin Group 3-minutes Post-NTG | Central Venous Pressure | 9.15 mmHg | Standard Deviation 3.25 |
| Topical Nitroglycerin Group 30-minutes Post-NTG | Central Venous Pressure | 9.16 mmHg | Standard Deviation 3.11 |
Secondary
Mean Arterial Pressure
Mean arterial blood pressure
Time frame: MAP was recorded for the control group, then for the NTG group at postoperative baseline, 3-minutes and 30-minutes after topical NTG application.
Population: Same groups as the primary outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Preoperative Control Group | Mean Arterial Pressure | 95.85 mmHg | Standard Deviation 11.67 |
| Topical Nitroglycerin Group Postop Baseline | Mean Arterial Pressure | 71.05 mmHg | Standard Deviation 5.92 |
| Topical Nitroglycerin Group 3-minutes Post-NTG | Mean Arterial Pressure | 70.35 mmHg | Standard Deviation 6.8 |
| Topical Nitroglycerin Group 30-minutes Post-NTG | Mean Arterial Pressure | 74.4 mmHg | Standard Deviation 7.19 |