Ketorolac for Postoperative Pain in Pediatric Heart Surgery

(CIVIK Trial)

Overseen By Samantha Stack, BS

Age: < 18

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: Phoenix Children's Hospital

Must not be taking: NSAIDs

Disqualifiers: Acute kidney injury, ECMO, others

Prior Safety Data

Approved in 5 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial tests if giving ketorolac through an IV can reduce the need for opiates in children after heart surgery. The goal is to find a safer way to manage pain and reduce the risks associated with opiates. Ketorolac is a nonsteroidal anti-inflammatory drug (NSAID) with potent pain-relieving effects and a relatively low incidence of adverse effects, often used to reduce opioid use and manage postoperative pain in various surgical settings.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, since the trial involves ketorolac, you should discuss your current medications with the trial team to ensure there are no interactions.

What data supports the idea that Ketorolac for Postoperative Pain in Pediatric Heart Surgery is an effective drug?

The available research shows that Ketorolac is effective in managing postoperative pain in children after heart surgery. It provides excellent pain relief without the sedating side effects that come with opioid painkillers. Additionally, studies indicate that Ketorolac can reduce the need for opioids, which are stronger pain medications that can have more side effects. This means children may experience less drowsiness and other opioid-related issues. However, there are concerns about the risk of bleeding, which is why its use is sometimes limited. ^{1 2 3 4 5}

What safety data exists for ketorolac in postoperative pain management?

Ketorolac, also known as Toradol, has been studied for its safety and efficacy in postoperative pain management. It is a nonsteroidal anti-inflammatory drug (NSAID) that can reduce the need for narcotics. However, it may increase the risk of bleeding and hematoma formation, as seen in studies involving breast surgery and microvascular thrombosis models. In pediatric orthopaedic patients, ketorolac reduced morphine use without significant adverse effects. Intranasal ketorolac has also been evaluated for safety and efficacy in postoperative pain. Overall, while ketorolac is effective in pain management, its potential to prolong bleeding times and cause hematomas should be considered. ^{1 5 6 7 8}

Is the drug used in the trial 'Ketorolac for Postoperative Pain in Pediatric Heart Surgery' promising?

Yes, ketorolac is a promising drug for managing postoperative pain. It provides effective pain relief without the sedating effects of opioids, and it can reduce the need for narcotic painkillers, which can have more side effects. ^{1 3 5 7 9}

Research Team

Kevin Engelhardt, MD

Principal Investigator

Heart Center

Eligibility Criteria

This trial is for children aged 3 months to 4 years who have had heart surgery and are in the pediatric cardiovascular ICU. They must start the study medication within two days after surgery. Kids with NSAID allergies, recent heart transplants, significant bleeding, kidney injuries or needing intensive support like ECMO or CRRT can't participate.

Inclusion Criteria

My child is between 3 months and 4 years old and was admitted to the CVICU after surgery.

I started the study medication within 48 hours after surgery.

Exclusion Criteria

I have had serious bleeding issues recently.

I needed heart or kidney support machines right after surgery.

You have had a bad reaction to ketorolac or other similar pain medications in the past.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either continuous infusion of ketorolac or intermittent ketorolac for postoperative pain control

48 hours

Continuous monitoring in CVICU

Follow-up

Participants are monitored for safety and effectiveness after treatment, including pain scores and sedative requirements

4 days

Treatment Details

Interventions

• Ketorolac (Nonsteroidal Anti-inflammatory Drug)

Trial Overview The study is testing if giving ketorolac continuously through an IV works better for pain control than giving it in separate doses (intermittently) after pediatric heart surgery. It's a controlled experiment where neither doctors nor patients know who gets which treatment to fairly compare outcomes.

Participant Groups

Group I: Treatment Experimental Treatment 1 Intervention

1. Description: Patients randomized for the treatment arm of the study group will receive a continuous infusion of ketorolac plus an intermittent dose of placebo (plasmalyte). To eliminate excess exposure and the associated side effects, all patients enrolled in the study will not be given any additional NSAIDs (except aspirin, which is standard of care in many post-operative cardiac surgery patients) during the study period. 2. Dosage and Route of Administration: 1. Continuous ketorolac 0.08mg/kg/hr, with a maximum of 5mg/hr for patients weighing greater than or equal to 60kg, administered intravenously by nursing staff. Study drug will infuse continuously for 48 hours. 2. Intermittent Plasmalyte 0.033mL/kg (max 2mL) infusion every 6 hours for 48 hours.

Group II: Standard of care Placebo Group 1 Intervention

1. Description: Patients randomized to the standard of care arm of the study will receive a generically marked syringe of Plasmalyte to be infused at the same rate as the treatment medication, and will only receive intermittent dosing of ketorolac (current standard of care). As in the treatment group, no additional NSAIDs (except aspirin) are to be given during the 48 hour study period. 2. Dosage and Route of Administration 1. Continuous Plasmalyte infusion to match the aforementioned ketorolac dosing 2. Intermittent ketorolac 0.5mg/kg IV infusion every 6 hours (max 30mg per dose)

Who Is Running the Clinical Trial?

Phoenix Children's Hospital

Lead Sponsor

Trials

78

Recruited

5,014,000+

Findings from Research

In a retrospective study of breast surgery patients over three years, ketorolac did not significantly increase the risk of postoperative hematoma formation, with rates of 3.5% in those receiving ketorolac compared to 2.5% in those who did not.

The overall hematoma rate for the entire cohort was 2.8%, suggesting that ketorolac can be safely used for postoperative pain control without raising concerns about bleeding complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toradol following Breast Surgery: Is There an Increased Risk of Hematoma? Nguyen, BN., Barta, RJ., Stewart, CE., et al.[2021]

In a study of 248 children who underwent low-risk cardiac surgery, ketorolac did not significantly affect renal function, as indicated by similar changes in serum creatinine levels between those who received ketorolac and those who did not.

Children who received ketorolac post-surgery required less opioid medication for pain management compared to the control group, suggesting that ketorolac may effectively reduce opioid use in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of ketorolac in children after cardiac surgery. Inoue, M., Caldarone, CA., Frndova, H., et al.[2021]

In a study involving 70 infants and children who underwent congenital heart surgery, ketorolac was found to effectively manage postoperative pain without increasing the risk of bleeding complications compared to opioid analgesics alone.

The results showed that patients receiving ketorolac had lower median chest-tube drainage and no significant wound bleeding, indicating its safety and efficacy as a pain management option in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective randomized trial of ketorolac after congenital heart surgery. Gupta, A., Daggett, C., Drant, S., et al.[2019]

A study reviewing 842 infants and children who underwent congenital heart surgery found that postoperative use of ketorolac did not significantly increase the risk of bleeding complications, with 0% of ketorolac patients requiring surgical exploration compared to 4.2% in the non-ketorolac group.

The relative risk of postoperative bleeding requiring surgical intervention in patients receiving ketorolac was 0.2, indicating that ketorolac can be safely used without a significant increase in bleeding risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketorolac after congenital heart surgery: does it increase the risk of significant bleeding complications? Gupta, A., Daggett, C., Ludwick, J., et al.[2013]

In a study of 27 pediatric patients undergoing orthopedic surgeries, ketorolac significantly reduced the need for morphine compared to a control group, indicating its effectiveness in managing postoperative pain.

Patients receiving ketorolac experienced fewer gastrointestinal side effects and had a shorter hospital stay, demonstrating that it is a safe alternative to morphine for pain management in pediatric orthopedic patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of ketorolac in decreasing length of stay and narcotic complications in the postoperative pediatric orthopaedic patient. Eberson, CP., Pacicca, DM., Ehrlich, MG.[2013]

A single dose of ketorolac significantly prolonged bleeding times and reduced platelet aggregation in a rat model, indicating its strong anti-thrombotic effects immediately after administration.

Despite its initial effectiveness in preventing thrombosis, ketorolac was ineffective for long-term prevention of microarterial thrombosis, and its use may pose a risk of bleeding complications in postoperative patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of ketorolac tromethamine (Toradol) on a functional model of microvascular thrombosis. Buckley, RC., Davidson, SF., Das, SK.[2019]

Ketorolac tromethamine is an effective nonsteroidal anti-inflammatory drug (NSAID) for managing moderate to severe postoperative pain, reducing the need for opioid analgesics, which can help minimize opioid-related side effects.

Administered intramuscularly, ketorolac reaches peak plasma levels in about 45 to 50 minutes and has a low incidence of side effects, making it a promising option for both inpatient and outpatient pain management, although further research is needed to fully understand its role.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketorolac: a new parenteral nonsteroidal anti-inflammatory drug for postoperative pain management. Lassen, K., Epstein-Stiles, M., Olsson, GL.[2013]

In a study of 127 patients undergoing major surgery, intranasal ketorolac at a dose of 31.5 mg significantly reduced the need for supplemental morphine compared to placebo and the lower 10 mg dose, indicating its efficacy in managing postoperative pain.

The 31.5 mg dose of ketorolac also resulted in lower rates of pyrexia and tachycardia compared to placebo, suggesting a better safety profile while effectively controlling pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety and analgesic efficacy of intranasal ketorolac in patients with postoperative pain. Moodie, JE., Brown, CR., Bisley, EJ., et al.[2013]

In a study involving 176 postoperative patients, ketorolac (10 mg orally) provided analgesic efficacy comparable to both 5 mg and 10 mg doses of morphine, significantly outperforming placebo.

Ketorolac is a safe and effective option for managing acute postoperative pain, serving as a non-opioid alternative to traditional opioid therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of ketorolac in the management of postoperative pain. DeAndrade, JR., Maslanka, M., Maneatis, T., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Toradol following Breast Surgery: Is There an Increased Risk of Hematoma? [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Safety and efficacy of ketorolac in children after cardiac surgery. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Prospective randomized trial of ketorolac after congenital heart surgery. [2019]

4. France pubmed.ncbi.nlm.nih.gov

Ketorolac after congenital heart surgery: does it increase the risk of significant bleeding complications? [2013]

5. United States pubmed.ncbi.nlm.nih.gov

The role of ketorolac in decreasing length of stay and narcotic complications in the postoperative pediatric orthopaedic patient. [2013]

6. England pubmed.ncbi.nlm.nih.gov

Effects of ketorolac tromethamine (Toradol) on a functional model of microvascular thrombosis. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Ketorolac: a new parenteral nonsteroidal anti-inflammatory drug for postoperative pain management. [2013]

8. United States pubmed.ncbi.nlm.nih.gov

The safety and analgesic efficacy of intranasal ketorolac in patients with postoperative pain. [2013]

9. United States pubmed.ncbi.nlm.nih.gov

The use of ketorolac in the management of postoperative pain. [2022]