Continuous Infusion Versus Bolus Dosing for Pain Control After Pediatric Cardiothoracic Surgery

The investigators hypothesize that intermittent bolus doses of morphine and midazolam can provide the same pain control after pediatric cardiothoracic surgery as bolus doses plus infusions while using smaller total doses of both medications.

The investigators will randomize patients to receive either morphine/midazolam as needed intermittently or morphine/midazolam drips plus intermittent doses to be received as needed. Pain scores will be recorded and total medications given will be recorded.

Study Overview

• Status: Completed
• Conditions: Congenital Heart Disease
• Intervention / Treatment: Drug: continuous infusion; Drug: Acetaminophen; Drug: ketorolac; Drug: as needed dosing

Detailed Description

Prior to surgery, eligible patients scheduled for surgery will be sent our standard surgery letter (Attachment A) along with our study informational sheet (Attachment B) describing our study. The study informational sheet will have a telephone number to call to set up a phone appointment to discuss the study with the PI should parents have questions not answered on the sheet. During the pre-operative visit, the study will again be discussed with the parents. Our nurse practitioners will be trained on this study and will obtain written consent at this time. If the parents would like to further discuss the study directly with the PI, this will be arranged prior to surgery.

The PI will be notified by the NPs of all parents who give permission for their child to participate in the study, and he will notify the on service medical team. On the day of surgery, a computerized order for the study will be entered to notify the pharmacy to randomize the subject to the control or treatment group. Randomization will be stratified based on whether the child has DS, as children with DS are known to have a heightened pain response and require large doses of medication to treat pain. Only the pharmacist will know the random assignment, health care providers and subjects/families will be blinded as to treatment arm.

Treatment Group:

Intravenous (IV) drip of 0.03 mg/kg/hour morphine and 0.03 mg/kg/hour midazolam

Control Group:

IV drip of normal saline (NS) at same volume as what the morphine/midazolam drip would be

Both Groups

Subjects in both the control and treatment group will receive the following post-operative pain control orders that are currently in use in the PSHU:

1. Morphine 0.05 mg/kg/dose IV q 2 hours prn pain score 4 or greater
2. Midazolam 0.05 mg/kg/dose IV q1 hours prn agitation
3. Additional prn doses of morphine and midazolam may be given as determined by the treating team (these doses will be recorded in the EMR)
4. Acetaminophen 30 mg/kg PR x 1 to be given on admission to PSHU post surgery
5. Acetaminophen 15 mg/kg PR q4 hours to be started 4 hours after first dose
6. Acetaminophen 15 mg/kg PO q4 hours to be started after subject starts drinking by mouth and PR doses stopped
7. Ketorolac 0.5 mg/kg/dose IV q 6 hours to start 6-12 hours after surgery when chest tube drainage criteria are met. Will start when chest tube drainage is no longer frankly bloody and if chest tube drainage is less than 3 cc/kg/hour for two hours in a row

• Study Type: Interventional
• Enrollment (Actual): 78
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Oak Lawn, Illinois, United States, 60453
      • Advocate Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 months to 4 months (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 3 months - 4 years (48 months)
• Anticipated cardiothoracic surgery with midline sternotomy incision
• Planned early extubation (e.g. within 3 hours post surgery)

Exclusion Criteria:

• Presence of renal insufficiency defined as a creatinine greater than 0.8mg/dL on the standard basic metabolic profile sent after surgery or history of chronic renal failure.
• Significant development delay that the bedside nurse or treating physician judges would make pain scoring difficult (Down syndrome is not excluded)
• History of bleeding disorder or gastrointestinal bleed within the past 2 months.
• Presence of chronic hepatic disease or elevation of AST or ALT greater than 250 U/L before or after surgery.
• More than 3 previous surgeries with a sternotomy incision (this may alter pain perception).
• Children on immunosuppressants

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Continuous infusion; Patients in this group will received morphine/midazolam drips at 0.3 mg/kg/hour each. They will be given doses of morphine 0.05 mg/kg/dose every 2 hours as needed for pain score 4 or more. Midazolam will also be given as needed (0.05 mg/kg/dose every 1 hour)	Drug: continuous infusion; Continuous morphine/midazolam and 'as needed' doses. Will receive scheduled acetaminophen and ketorolac.; Other Names: acetaminophen and ketorolac are scheduled for this arm of the study; Drug: Acetaminophen; Acetaminophen will be given every 4 hours for a total of 24 hours.; Drug: ketorolac; Ketorolac 0.5 mg/kg will be given every six hours to all subjects in the study.
Active Comparator: As needed dosing; Patients in this arm will be given doses of morphine 0.05 mg/kg/dose every 2 hours as needed for pain score 4 or more. Midazolam will also be given as needed (0.05 mg/kg/dose every 1 hour)	Drug: Acetaminophen; Acetaminophen will be given every 4 hours for a total of 24 hours.; Drug: ketorolac; Ketorolac 0.5 mg/kg will be given every six hours to all subjects in the study.; Drug: as needed dosing; morphine and midazolam as needed. Will receive scheduled acetaminophen and ketorolac..; Other Names: acetaminophen and ketorolac are both scheduled for this arm as well

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Morphine Dosage	Total dose of morphine used will be recorded for each patient.	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of Stay	Length of stay will be recorded for each subject.	From date of randomization until the date of first documented progression or date of death from any cause or discharge, whichever came first, assessed up to 100 months

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Investigators: Principal Investigator: Jamie S Penk, Advocate Children's Hospital

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Actual): May 1, 2016
• Study Completion (Actual): May 1, 2016

Study Registration Dates

• First Submitted: March 28, 2014
• First Submitted That Met QC Criteria: April 10, 2014
• First Posted (Estimated): April 14, 2014

Study Record Updates

• Last Update Posted (Actual): October 24, 2024
• Last Update Submitted That Met QC Criteria: October 22, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: congenital heart disease, pediatric cardiothoracic surgery
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Heart Diseases; Heart Defects, Congenital; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Antirheumatic Agents; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Antipyretics; Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase Inhibitors; Acetaminophen; Ketorolac; Ketorolac Tromethamine
• Other Study ID Numbers: K5900208

Plan for Individual participant data (IPD)

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