Papaverine vs Heparin for Peripheral Arterial Catheter Patency in Pediatric Patients

Double-Blind, Randomized, Controlled Trial, Small Volume Bolus of Papaverine Versus Heparin to Maintain Patency of Peripheral Arterial Catheters in Pediatric Patients Undergoing Surgical Procedures: Pilot Study

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.

Study Overview

• Status: Completed
• Conditions: Anesthesia; Pediatrics; Vasospasm
• Intervention / Treatment: Drug: Papaverine; Drug: Heparin; Drug: Rescue papaverine, as needed

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.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • UT Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: 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; Drug: 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; Drug: 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.
Active Comparator: 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.	Drug: 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; Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	5 minutes after first dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	60 minutes after first dose
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.	5 minutes after injection of rescue papaverine (about 70 minutes after first study drug dose and about 10 minutes after second study drug dose)

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center, Houston
• Investigators: Study Director: Nischal K Gautam, MD, UTHealth

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2019
• Primary Completion (Actual): October 10, 2020
• Study Completion (Actual): October 10, 2020

Study Registration Dates

• First Submitted: March 27, 2019
• First Submitted That Met QC Criteria: March 27, 2019
• First Posted (Actual): March 29, 2019

Study Record Updates

• Last Update Posted (Actual): October 27, 2022
• Last Update Submitted That Met QC Criteria: October 26, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Heparin; Papaverine
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Urological Agents; Enzyme Inhibitors; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Phosphodiesterase Inhibitors; Heparin; Papaverine
• Other Study ID Numbers: HSC-MS-19-0059

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No