Trial Outcomes & Findings for Continuous Infusion Versus Bolus Dosing for Pain Control After Pediatric Cardiothoracic Surgery (NCT NCT02112448)

Results Overview

Total dose of morphine used will be recorded for each patient.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

78 participants

Primary outcome timeframe

24 hours

Results posted on

2024-10-24

Participant Flow

We enrolled 78, but 18 were excluded after informed consent for the reasons listed below. 30 in each group were assigned and completed the study.

Participant milestones

Participant milestones
Measure	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) as needed dosing: This group will receive morphine and midazolam as needed to control their pain. Acetaminophen and ketorolac will also be given for pain control in the same manner as the continuous infusion group. Acetaminophen: Acetaminophen will be given as a loading dose of 30 mg/kg rectally post surgery to all subjects and then 15 mg/kg every 4 hours for a total of 24 hours. ketorolac: Ketorolac 0.5 mg/kg will be given every six hours to all subjects in the study.	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) continuous infusion: This arm will receive continuous morphine/midazolam and 'as needed' doses. This group will receive adjunctive medications, acetaminophen and ketorolac. Acetaminophen: Acetaminophen will be given as a loading dose of 30 mg/kg rectally post surgery to all subjects and then 15 mg/kg every 4 hours for a total of 24 hours. ketorolac: Ketorolac 0.5 mg/kg will be given every six hours to all subjects in the study.
Overall Study STARTED	38	40
Overall Study COMPLETED	30	30
Overall Study NOT COMPLETED	8	10

Reasons for withdrawal

Reasons for withdrawal
Measure	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) as needed dosing: This group will receive morphine and midazolam as needed to control their pain. Acetaminophen and ketorolac will also be given for pain control in the same manner as the continuous infusion group. Acetaminophen: Acetaminophen will be given as a loading dose of 30 mg/kg rectally post surgery to all subjects and then 15 mg/kg every 4 hours for a total of 24 hours. ketorolac: Ketorolac 0.5 mg/kg will be given every six hours to all subjects in the study.	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) continuous infusion: This arm will receive continuous morphine/midazolam and 'as needed' doses. This group will receive adjunctive medications, acetaminophen and ketorolac. Acetaminophen: Acetaminophen will be given as a loading dose of 30 mg/kg rectally post surgery to all subjects and then 15 mg/kg every 4 hours for a total of 24 hours. ketorolac: Ketorolac 0.5 mg/kg will be given every six hours to all subjects in the study.
Overall Study lab values precluding use of ketorolac	2	2
Overall Study Protocol Violation	1	2
Overall Study Physician Decision	4	6
Overall Study required heparin so could not use ketoro	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Continuous Infusion n=30 Participants 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) continuous infusion: This arm will receive continuous morphine/midazolam and 'as needed' doses. This group will receive adjunctive medications, acetaminophen and ketorolac. Acetaminophen: Acetaminophen will be given as a loading dose of 30 mg/kg rectally post surgery to all subjects and then 15 mg/kg every 4 hours for a total of 24 hours. ketorolac: Ketorolac 0.5 mg/kg will be given every six hours to all subjects in the study.	As Needed Dosing n=30 Participants 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) as needed dosing: This group will receive morphine and midazolam as needed to control their pain. Acetaminophen and ketorolac will also be given for pain control in the same manner as the continuous infusion group. Acetaminophen: Acetaminophen will be given as a loading dose of 30 mg/kg rectally post surgery to all subjects and then 15 mg/kg every 4 hours for a total of 24 hours. ketorolac: Ketorolac 0.5 mg/kg will be given every six hours to all subjects in the study.	Total n=60 Participants Total of all reporting groups
Age, Continuous	14.8 months STANDARD_DEVIATION 12.1 • n=113 Participants	16 months STANDARD_DEVIATION 12.8 • n=163 Participants	15.4 months STANDARD_DEVIATION 12.5 • n=160 Participants
Sex: Female, Male Female	17 Participants n=113 Participants	18 Participants n=163 Participants	35 Participants n=160 Participants
Sex: Female, Male Male	13 Participants n=113 Participants	12 Participants n=163 Participants	25 Participants n=160 Participants
Presence of Down syndrome	5 Participants n=113 Participants	4 Participants n=163 Participants	9 Participants n=160 Participants
Surgical complexity scores	59 units on a scale n=113 Participants	61 units on a scale n=163 Participants	120 units on a scale n=160 Participants

PRIMARY outcome

Timeframe: 24 hours

Total dose of morphine used will be recorded for each patient.

Outcome measures

Outcome measures
Measure	Continuous Infusion n=30 Participants 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) continuous infusion: This arm will receive continuous morphine/midazolam and 'as needed' doses. This group will receive adjunctive medications, acetaminophen and ketorolac. Acetaminophen: Acetaminophen will be given as a loading dose of 30 mg/kg rectally post surgery to all subjects and then 15 mg/kg every 4 hours for a total of 24 hours. ketorolac: Ketorolac 0.5 mg/kg will be given every six hours to all subjects in the study.	As Needed Dosing n=30 Participants 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) as needed dosing: This group will receive morphine and midazolam as needed to control their pain. Acetaminophen and ketorolac will also be given for pain control in the same manner as the continuous infusion group. Acetaminophen: Acetaminophen will be given as a loading dose of 30 mg/kg rectally post surgery to all subjects and then 15 mg/kg every 4 hours for a total of 24 hours. ketorolac: Ketorolac 0.5 mg/kg will be given every six hours to all subjects in the study.
Total Morphine Dosage	0.9 mg/kg Standard Deviation 0.13	0.23 mg/kg Standard Deviation 0.14

SECONDARY outcome

Timeframe: 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

Length of stay will be recorded for each subject.

Outcome measures

Outcome measures
Measure	Continuous Infusion n=30 Participants 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) continuous infusion: This arm will receive continuous morphine/midazolam and 'as needed' doses. This group will receive adjunctive medications, acetaminophen and ketorolac. Acetaminophen: Acetaminophen will be given as a loading dose of 30 mg/kg rectally post surgery to all subjects and then 15 mg/kg every 4 hours for a total of 24 hours. ketorolac: Ketorolac 0.5 mg/kg will be given every six hours to all subjects in the study.	As Needed Dosing n=30 Participants 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) as needed dosing: This group will receive morphine and midazolam as needed to control their pain. Acetaminophen and ketorolac will also be given for pain control in the same manner as the continuous infusion group. Acetaminophen: Acetaminophen will be given as a loading dose of 30 mg/kg rectally post surgery to all subjects and then 15 mg/kg every 4 hours for a total of 24 hours. ketorolac: Ketorolac 0.5 mg/kg will be given every six hours to all subjects in the study.
Length of Stay	4.9 days Standard Deviation 2.5	8.4 days Standard Deviation 7.7

Adverse Events

As Needed Dosing

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Continuous Infusion

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	As Needed Dosing n=38 participants at risk 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) as needed dosing: This group will receive morphine and midazolam as needed to control their pain. Acetaminophen and ketorolac will also be given for pain control in the same manner as the continuous infusion group. Acetaminophen: Acetaminophen will be given as a loading dose of 30 mg/kg rectally post surgery to all subjects and then 15 mg/kg every 4 hours for a total of 24 hours. ketorolac: Ketorolac 0.5 mg/kg will be given every six hours to all subjects in the study.	Continuous Infusion n=40 participants at risk 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) continuous infusion: This arm will receive continuous morphine/midazolam and 'as needed' doses. This group will receive adjunctive medications, acetaminophen and ketorolac. Acetaminophen: Acetaminophen will be given as a loading dose of 30 mg/kg rectally post surgery to all subjects and then 15 mg/kg every 4 hours for a total of 24 hours. ketorolac: Ketorolac 0.5 mg/kg will be given every six hours to all subjects in the study.
Cardiac disorders Severe adverse event	0.00% 0/38	2.5% 1/40 • Number of events 1

Other adverse events

Other adverse events
Measure	As Needed Dosing n=38 participants at risk 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) as needed dosing: This group will receive morphine and midazolam as needed to control their pain. Acetaminophen and ketorolac will also be given for pain control in the same manner as the continuous infusion group. Acetaminophen: Acetaminophen will be given as a loading dose of 30 mg/kg rectally post surgery to all subjects and then 15 mg/kg every 4 hours for a total of 24 hours. ketorolac: Ketorolac 0.5 mg/kg will be given every six hours to all subjects in the study.	Continuous Infusion n=40 participants at risk 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) continuous infusion: This arm will receive continuous morphine/midazolam and 'as needed' doses. This group will receive adjunctive medications, acetaminophen and ketorolac. Acetaminophen: Acetaminophen will be given as a loading dose of 30 mg/kg rectally post surgery to all subjects and then 15 mg/kg every 4 hours for a total of 24 hours. ketorolac: Ketorolac 0.5 mg/kg will be given every six hours to all subjects in the study.
Cardiac disorders Hypotension	0.00% 0/38	2.5% 1/40 • Number of events 1
Respiratory, thoracic and mediastinal disorders Respiratory depression	0.00% 0/38	2.5% 1/40 • Number of events 1
Nervous system disorders Paradoxical reaction to midazolam	2.6% 1/38 • Number of events 1	0.00% 0/40
Nervous system disorders Inadequate pain control	2.6% 1/38 • Number of events 1	0.00% 0/40
Hepatobiliary disorders Large dose of acetaminophen given	2.6% 1/38 • Number of events 1	0.00% 0/40

Additional Information

Jamie Penk

Advocate Children's Hospital

Phone: 7086845580

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place