Pediatrics, Anesthesia, Vasospasm
Conditions
Keywords
Heparin, Papaverine
Brief summary
The purpose of this study is to compare intraoperative papaverine plus heparin to heparin alone for prevention of arterial spasm and maintenance of patency of peripheral arterial catheters during surgery in pediatric patients. The hypothesis is that periodic, intraoperative small-volume boluses of diluted papaverine plus heparin in peripheral arterial catheters of pediatric patients will prevent arterial spasm and help maintain patency of arterial catheters during general anesthesia.
Detailed description
Peripheral arterial catheters measure blood pressure with every heartbeat and provide valuable information regarding the status of the heart and the overall well being. It is of utmost importance to maintain the utility and patency of these catheters throughout the procedure. As standard procedure, heparin, a blood thinner, is used routinely during the surgical procedure to keep these catheters from clotting, and papaverine, an arterial relaxation agent, is used after surgery to maintain patency of these catheters. In this study, participants will be randomized to receive two boluses of papaverine with heparin during the procedure (experimental arm) or heparin alone during the procedure (control arm) \[in both arms, the first bolus will be administered as soon as the arterial catheter is placed and secured and again one hour after initial bolus\]. If the arterial catheter spasm/patency or waveform does not improve 10 minutes after the second bolus, then the anesthesiology care team will consider treating clinically with 0.3 mg of papaverine.
Interventions
DRUGPapaverine
0.12 mg/mL papaverine administered as soon as the arterial catheter is placed and secured, and 0.12 mg/mL papaverine administered one hour after initial dose
DRUGHeparin
2 units/mL heparin administered as soon as the arterial catheter is placed and secured, and 2 units/mL heparin administered one hour after initial dose
DRUGRescue papaverine, as needed
If the arterial catheter spasm/patency or waveform does not improve 10 minutes after the second papaverine plus heparin or heparin only dose, then the anesthesiology care team will consider treating clinically with 0.3 mg of papaverine.
Sponsors
The University of Texas Health Science Center, Houston
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
No minimum to 17 Years
Healthy volunteers
No
Inclusion criteria
\- All patients age 0-17 years who would require elective placements of arterial catheters based on patients clinical complexity (ex. congenital heart disease) or based on the type of surgery (ex. open heart surgery).
Exclusion criteria
* Patients with a history of significant liver dysfunction. * Patients undergoing liver transplants. * Patients with Grade 2 or more of intraventricular hemorrhage. * All preterm patients with a gestational age less than 37 weeks at the time of surgery.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Optimal Arterial Waveform | 5 minutes after first dose | Optimal waveform was defined as easy aspiration of a blood sample (negative aspiration is easy and draws back freely without cavitation, and takes no more than 30 seconds to draw 1 mL), absence of color change at the catheter insertion site, and presence of a dicrotic notch in the arterial pressure waveform (a distinct dicrotic notch implies system has good resolution at higher frequencies and is not overdamped). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Optimal Arterial Waveform | 60 minutes after first dose | Optimal waveform was defined as easy aspiration of a blood sample (negative aspiration is easy and draws back freely without cavitation, and takes no more than 30 seconds to draw 1 mL), absence of color change at the catheter insertion site, and presence of a dicrotic notch in the arterial pressure waveform (a distinct dicrotic notch implies system has good resolution at higher frequencies and is not overdamped). |
| Number of Participants With Suboptimal Waveforms Who Received Rescue Papaverine and for Whom Papaverine Rescued Suboptimal Waveforms | 5 minutes after injection of rescue papaverine (about 70 minutes after first study drug dose and about 10 minutes after second study drug dose) | These data were collected only from participants who received rescue papaverine. 7 in the Papaverine plus Heparin arm received rescue papaverine. 17 in the Heparin arm received rescue papaverine. |
Countries
United States
Participant flow
Pre-assignment details
4 enrolled participants declined to participate before being assigned to an intervention and therefore did not receive the intervention.
Participants by arm
| Arm | Count |
|---|---|
| Papaverine Plus Heparin During Procedure, With Rescue Papaverine as Needed 1 mL bolus of papaverine (0.12 mg/mL) plus heparin (2 units/mL) in saline (NaCl 0.9%) will be administered as soon as the arterial catheter is placed and secured, and a 1 mL bolus of papaverine (0.12 mg/mL) plus heparin (2 units/mL) in saline (NaCl 0.9%) will be administered one hour after initial bolus. If the arterial catheter spasm/patency or waveform does not improve 10 minutes after the second bolus, then the anesthesiology care team will consider treating clinically with 0.3 mg of papaverine.
Papaverine: 0.12 mg/mL papaverine administered as soon as the arterial catheter is placed and secured, and 0.12 mg/mL papaverine administered one hour after initial dose
Heparin: 2 units/mL heparin administered as soon as the arterial catheter is placed and secured, and 2 units/mL heparin administered one hour after initial dose
Rescue papaverine, as needed: If the arterial catheter spasm/patency or waveform does not improve 10 minutes after the second papaverine plus heparin or heparin only dose, then the anesthesiology care team will consider treating clinically with 0.3 mg of papaverine. | 42 |
| Heparin During Procedure, With Rescue Papaverine as Needed 1 mL bolus of heparin (2 units/mL) in saline (NaCl 0.9%) will be administered as soon as the arterial catheter is placed and secured, and a 1 mL bolus of heparin (2 units/mL) in saline (NaCl 0.9%) will be administered one hour after initial bolus. If the arterial catheter spasm/patency or waveform does not improve 10 minutes after the second bolus, then the anesthesiology care team will consider treating clinically with 0.3 mg of papaverine.
Heparin: 2 units/mL heparin administered as soon as the arterial catheter is placed and secured, and 2 units/mL heparin administered one hour after initial dose
Rescue papaverine, as needed: If the arterial catheter spasm/patency or waveform does not improve 10 minutes after the second papaverine plus heparin or heparin only dose, then the anesthesiology care team will consider treating clinically with 0.3 mg of papaverine. | 46 |
| Total | 88 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Randomized Dosing (Doses 1 and 2) | Did not receive intervention because peripheral arterial line (PAL) was replaced due to spasm | 2 | 3 |
| Randomized Dosing (Doses 1 and 2) | Did not receive second dose | 2 | 1 |
Baseline characteristics
| Characteristic | Heparin During Procedure, With Rescue Papaverine as Needed | Total | Papaverine Plus Heparin During Procedure, With Rescue Papaverine as Needed |
|---|---|---|---|
| Age, Continuous | 24.7 months STANDARD_DEVIATION 39.5 | 24.5 months STANDARD_DEVIATION 43 | 24.1 months STANDARD_DEVIATION 46.9 |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment United States | 46 Participants | 88 Participants | 42 Participants |
| Sex: Female, Male Female | 20 Participants | 40 Participants | 20 Participants |
| Sex: Female, Male Male | 26 Participants | 48 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 42 | 0 / 46 |
| other Total, other adverse events | 0 / 42 | 0 / 46 |
| serious Total, serious adverse events | 0 / 42 | 0 / 46 |
Outcome results
Primary
Number of Participants With Optimal Arterial Waveform
Optimal waveform was defined as easy aspiration of a blood sample (negative aspiration is easy and draws back freely without cavitation, and takes no more than 30 seconds to draw 1 mL), absence of color change at the catheter insertion site, and presence of a dicrotic notch in the arterial pressure waveform (a distinct dicrotic notch implies system has good resolution at higher frequencies and is not overdamped).
Time frame: 5 minutes after first dose
Population: These data were not collected for 2 participants in the Papaverine plus Heparin arm and 1 in the Heparin arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Papaverine Plus Heparin During Procedure, With Rescue Papaverine as Needed | Number of Participants With Optimal Arterial Waveform | 27 Participants |
| Heparin During Procedure, With Rescue Papaverine as Needed | Number of Participants With Optimal Arterial Waveform | 18 Participants |
Secondary
Number of Participants With Optimal Arterial Waveform
Optimal waveform was defined as easy aspiration of a blood sample (negative aspiration is easy and draws back freely without cavitation, and takes no more than 30 seconds to draw 1 mL), absence of color change at the catheter insertion site, and presence of a dicrotic notch in the arterial pressure waveform (a distinct dicrotic notch implies system has good resolution at higher frequencies and is not overdamped).
Time frame: 60 minutes after first dose
Population: These data were not collected for 2 participants in the Papaverine plus Heparin arm and 1 in the Heparin arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Papaverine Plus Heparin During Procedure, With Rescue Papaverine as Needed | Number of Participants With Optimal Arterial Waveform | 30 Participants |
| Heparin During Procedure, With Rescue Papaverine as Needed | Number of Participants With Optimal Arterial Waveform | 28 Participants |
Secondary
Number of Participants With Suboptimal Waveforms Who Received Rescue Papaverine and for Whom Papaverine Rescued Suboptimal Waveforms
These data were collected only from participants who received rescue papaverine. 7 in the Papaverine plus Heparin arm received rescue papaverine. 17 in the Heparin arm received rescue papaverine.
Time frame: 5 minutes after injection of rescue papaverine (about 70 minutes after first study drug dose and about 10 minutes after second study drug dose)
Population: These data were collected only from participants who received rescue papaverine. 7 in the Papaverine plus Heparin arm received rescue papaverine. 17 in the Heparin arm received rescue papaverine.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Papaverine Plus Heparin During Procedure, With Rescue Papaverine as Needed | Number of Participants With Suboptimal Waveforms Who Received Rescue Papaverine and for Whom Papaverine Rescued Suboptimal Waveforms | 3 Participants |
| Heparin During Procedure, With Rescue Papaverine as Needed | Number of Participants With Suboptimal Waveforms Who Received Rescue Papaverine and for Whom Papaverine Rescued Suboptimal Waveforms | 13 Participants |