Pulmonary Arterial Hypertension
Conditions
Brief summary
Pulmonary arterial hypertension (PAH) is a disease where the blood pressure in the pulmonary arteries (PAP) is high. PAH increases the risk of adverse events, including death, during and or after procedures. The severity of baseline PAH correlates with the incidence of major complications, such that those with PAP higher than their systemic blood pressure (SBP) had a 8 fold increased risk of complications. These children present for procedures where an acute exacerbation of their chronic illness-termed Pulmonary Hypertensive (PH)crisis, can occur, often resulting in death if not detected and managed expeditiously. Unfortunately there is little data and no consensus in the pediatric literature on how PH crisis should be managed. \--------------------------------------------------------------------------------
Detailed description
Pulmonary arterial hypertension (PAH) is a disease where the blood pressure in the pulmonary arteries (PAP) is high. PAH increases the risk of adverse events, including death, during and or after procedures. The severity of baseline PAH correlates with the incidence of major complications, such that those with PAP higher than their systemic blood pressure (SBP) had a 8 fold increased risk of complications. These children present for procedures where an acute exacerbation of their chronic illness-termed PH crisis, can occur, often resulting in death if not detected and managed expeditiously. Unfortunately there is little data and no consensus in the pediatric literature on how PH crisis should be managed. Over the last 10 years we have developed considerable expertise in managing children with PAH and preventing and treating their acute crisis, using a medication called phenylephrine. This medication is routinely used to increase the blood pressure in patients (adults and children) to treat hypotension. Our theory has been that by increasing SBP, we can increase the blood flow to the coronary arteries and prevent the right ventricle from failing acutely. The latter results in catastrophic hypotension, heart arrythmias and death. There is no consensus or protocol guiding the management of the acute crisis. This purpose of this study is to close that gap.
Interventions
DRUGPhenylephrine
5 subjects will get Phenylephrine during cardiac catheterization in patient with known Pulmonary Arterial Hypertension.Dose will be 1ug/kg body weight. Pressures in the pulmonary artery will be measured before and after the drug administration.
DRUGEpinephrine
5 subjects will get Epinephrine during cardiac catheterization in patient with known Pulmonary Arterial Hypertension.Dose will be 0.5-1ug/kg body weight. Pressures in the pulmonary artery will be measured before and after the drug administration.
5 subjects will get Arginine Vasopressin during cardiac catheterization in patient with known Pulmonary Arterial Hypertension.Dose will be 1ug/kg body weight. Pressures in the pulmonary artery will be measured before and after the drug administration.
Sponsors
Stanford University
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
* Patients presenting for cardiac catheterization procedure with a diagnosis of PAH either by previous cardiac catheterization or echocardiography
Exclusion criteria
* Children presenting for cardiac catheterization who do not have PAH; * Children with PAH but with intracardiac shunts
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Systemic Vascular Resistance Index (SVRI) to Pulmonary Vascular Resistance Index (PVRI) Ratio (Rp:Rs Ratio) | Day 1 (at baseline and up to 5 minutes following study drug administration) (Q: 2 minutes - 2 to 5 minutes?) | In patients with pulmonary hypertension (PH) one anticipates a greater increase in pulmonary vascular resistance as opposed to systemic vascular resistance when vasopressors are administered. |
Countries
United States
Participant flow
Pre-assignment details
Participants were assigned sequentially; the first group received phenylephrine, the second group received arginine vasopressin, and the third group received epinephrine.
Participants by arm
| Arm | Count |
|---|---|
| Phenylephrine Phenylephrine (1ug/kg) administered once the child is under anesthesia. | 5 |
| Arginine Vasopressin Arginine Vasopressin (1ug/kg) administered once the child is under anesthesia. | 5 |
| Epinephrine Epinephrine (0.5-1ug/kg) administered once the child is under anesthesia. | 5 |
| Total | 15 |
Baseline characteristics
| Characteristic | Arginine Vasopressin | Epinephrine | Total | Phenylephrine |
|---|---|---|---|---|
| Age, Continuous | 10.5 years STANDARD_DEVIATION 4.9 | 6.8 years STANDARD_DEVIATION 4.2 | 9.2 years STANDARD_DEVIATION 4.5 | 10.2 years STANDARD_DEVIATION 3.8 |
| Race and Ethnicity Not Collected | — | — | 0 Participants | — |
| Region of Enrollment United States | 5 Participants | 5 Participants | 15 Participants | 5 Participants |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 11 Participants | 4 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 4 Participants | 1 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 / 5 | 0 / 5 |
| other Total, other adverse events | 0 / 5 | 0 / 5 | 2 / 5 |
| serious Total, serious adverse events | 0 / 5 | 0 / 5 | 0 / 5 |
Outcome results
Primary
Change in Systemic Vascular Resistance Index (SVRI) to Pulmonary Vascular Resistance Index (PVRI) Ratio (Rp:Rs Ratio)
In patients with pulmonary hypertension (PH) one anticipates a greater increase in pulmonary vascular resistance as opposed to systemic vascular resistance when vasopressors are administered.
Time frame: Day 1 (at baseline and up to 5 minutes following study drug administration) (Q: 2 minutes - 2 to 5 minutes?)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phenylephrine | Change in Systemic Vascular Resistance Index (SVRI) to Pulmonary Vascular Resistance Index (PVRI) Ratio (Rp:Rs Ratio) | Baseline | 0.8 Rp:Rs ratio | Standard Deviation 0.7 |
| Phenylephrine | Change in Systemic Vascular Resistance Index (SVRI) to Pulmonary Vascular Resistance Index (PVRI) Ratio (Rp:Rs Ratio) | Approx. 2 minutes following drug administration | 0.73 Rp:Rs ratio | Standard Deviation 0.77 |
| Arginine Vasopressin | Change in Systemic Vascular Resistance Index (SVRI) to Pulmonary Vascular Resistance Index (PVRI) Ratio (Rp:Rs Ratio) | Baseline | 0.75 Rp:Rs ratio | Standard Deviation 0.41 |
| Arginine Vasopressin | Change in Systemic Vascular Resistance Index (SVRI) to Pulmonary Vascular Resistance Index (PVRI) Ratio (Rp:Rs Ratio) | Approx. 2 minutes following drug administration | 0.49 Rp:Rs ratio | Standard Deviation 0.24 |
| Epinephrine | Change in Systemic Vascular Resistance Index (SVRI) to Pulmonary Vascular Resistance Index (PVRI) Ratio (Rp:Rs Ratio) | Baseline | 0.61 Rp:Rs ratio | Standard Deviation 0.23 |
| Epinephrine | Change in Systemic Vascular Resistance Index (SVRI) to Pulmonary Vascular Resistance Index (PVRI) Ratio (Rp:Rs Ratio) | Approx. 2 minutes following drug administration | 0.6 Rp:Rs ratio | Standard Deviation 0.34 |
Comparison: Change in phenylephrine groupp-value: 0.9t-test, 2 sided
Comparison: Change in arginine vasopressin groupp-value: 0.3t-test, 2 sided
Comparison: Change in epinephrine groupp-value: 1t-test, 2 sided