Continuous vs Intermittent Ketorolac for Pain Control in Peds CV Surgery

Congenital Heart Disease in Children Clinical Trial

Official title:

Continuous Infusion Versus Intermittent Ketorolac for Postoperative Pain Control in Pediatric Cardiac Surgery Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04040452
• Other study ID #: 166166
• Status: Recruiting
• Phase: Phase 4
• Start date: March 1, 2021
• Est. completion date: December 1, 2025

Study information

• Verified date: February 2024
• Source: Phoenix Children's Hospital
• Contact: Kevin Engelhardt, MD
• Phone: 6029333366
• Email: kengelhardt[@]phoenixchildrens.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The proposed study will be a prospective, randomized, double blind, placebo controlled trial to compare the use of a continuous infusion versus intermittent ketorolac on postoperative patients in the pediatric cardiovascular ICU. We intend to determine if the continuous infusion leads to a decreased utilization of opiates when compared to intermittent ketorolac.

Description:

The mainstay of postoperative pain control in the CVICU remains opiate-based therapy. Reliance on this class of medications can be detrimental, contributing to complications including hemodynamic instability, dependency, and withdrawal which can ultimately lead to longer hospital admissions, as well as long term and persistent neurodevelopmental effects. In addition, the opioid crisis has driven practitioners to aim for methods to reduce opioid exposure and post-operative narcotic prescriptions in pediatric and adult patients alike. There is a growing body of evidence in the adult literature showing promising results with the use of a continuous infusion of ketorolac in postoperative patients, including in a pediatric population. What the current literature has failed to show is whether a continuous infusion of ketorolac post operatively decreases the use of opiate mediations in a pediatric population compared to intermittent bolus injections, which is the current standard of care. Given the sensitivity and fragility inherent in those patients with CHD, working to reduce deleterious effects from excessive and prolonged opiate exposure is imperative. This study aims to examine whether the use of a continuous infusion of ketorolac can reduce the amount of opiates needed to treat postoperative pain control in the pediatric CVICU population, in comparison to patients who receive intermittent ketorolac within the first 72 hours post-operatively.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 166
• Est. completion date: December 1, 2025
• Est. primary completion date: January 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Months to 4 Years

Eligibility

Inclusion Criteria:

1. All patients aged 3 months to 4 years admitted post operatively to the CVICU during the time period in which the study will be ongoing

2. Initiation of study medication within the first 12-24 hours post-operatively

3. The cardiovascular attending of record after review of the intraoperative course and post-operative laboratories determines the patient will receive Ketorolac for pain control

Exclusion Criteria:

1. Patients that have acute kidney injury, as defined by the letter "I" in the pRIFLE criteria.

2. History of allergy or sensitivity reaction to ketorolac or any NSAID medications.

3. Requiring mechanical circulatory support (ECMO) or continuous renal replacement therapy (CRRT) within the first 48 hours post-operatively

4. Orthotopic heart transplantation

5. Clinically significant bleeding

6. Patients with known pre-operative medical renal disease, renal transplantation history, congenital or acquired renal abnormality or deformity

Related Conditions & MeSH terms

• Congenital Heart Disease in Children
• Heart Defects, Congenital
• Heart Diseases

Intervention

Drug:
• Continuous ketorolac
Patients randomized for the treatment arm of the study group will receive a continuous infusion of ketorolac plus an intermittent dose of placebo (plasmalyte) for 48 hours.

Locations

Country	Name	City	State
United States	Phoenix Children's Hospital	Phoenix	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Phoenix Children's Hospital

Country where clinical trial is conducted

United States, 

References & Publications (12)

Britton J, Martinez FD. The relationship of childhood respiratory infection to growth and decline in lung function. Am J Respir Crit Care Med. 1996 Dec;154(6 Pt 2):S240-5. doi: 10.1164/ajrccm/154.6_Pt_2.S240. No abstract available. — View Citation

Burd RS, Tobias JD. Ketorolac for pain management after abdominal surgical procedures in infants. South Med J. 2002 Mar;95(3):331-3. — View Citation

Burns JW, Aitken HA, Bullingham RE, McArdle CS, Kenny GN. Double-blind comparison of the morphine sparing effect of continuous and intermittent i.m. administration of ketorolac. Br J Anaesth. 1991 Sep;67(3):235-8. doi: 10.1093/bja/67.3.235. — View Citation

Cohen MN, Christians U, Henthorn T, Vu Tran Z, Moll V, Zuk J, Galinkin J. Pharmacokinetics of single-dose intravenous ketorolac in infants aged 2-11 months. Anesth Analg. 2011 Mar;112(3):655-60. doi: 10.1213/ANE.0b013e3182075d04. Epub 2011 Jan 13. — View Citation

Dawkins TN, Barclay CA, Gardiner RL, Krawczeski CD. Safety of intravenous use of ketorolac in infants following cardiothoracic surgery. Cardiol Young. 2009 Feb;19(1):105-8. doi: 10.1017/S1047951109003527. Epub 2009 Jan 12. — View Citation

Grimsby GM, Conley SP, Trentman TL, Castle EP, Andrews PE, Mihalik LA, Hentz JG, Humphreys MR. A double-blind randomized controlled trial of continuous intravenous Ketorolac vs placebo for adjuvant pain control after renal surgery. Mayo Clin Proc. 2012 Nov;87(11):1089-97. doi: 10.1016/j.mayocp.2012.07.018. Epub 2012 Oct 8. — View Citation

Gupta A, Daggett C, Drant S, Rivero N, Lewis A. Prospective randomized trial of ketorolac after congenital heart surgery. J Cardiothorac Vasc Anesth. 2004 Aug;18(4):454-7. doi: 10.1053/j.jvca.2004.05.024. — View Citation

Howard ML, Isaacs AN, Nisly SA. Continuous Infusion Nonsteroidal Anti-Inflammatory Drugs for Perioperative Pain Management. J Pharm Pract. 2018 Feb;31(1):66-81. doi: 10.1177/0897190016665539. Epub 2016 Aug 31. — View Citation

Inoue M, Caldarone CA, Frndova H, Cox PN, Ito S, Taddio A, Guerguerian AM. Safety and efficacy of ketorolac in children after cardiac surgery. Intensive Care Med. 2009 Sep;35(9):1584-92. doi: 10.1007/s00134-009-1541-1. Epub 2009 Jun 27. — View Citation

Jalkut MK. Ketorolac as an analgesic agent for infants and children after cardiac surgery: safety profile and appropriate patient selection. AACN Adv Crit Care. 2014 Jan-Mar;25(1):23-30; quiz 31-2. doi: 10.1097/NCI.0000000000000002. — View Citation

Moffett BS, Wann TI, Carberry KE, Mott AR. Safety of ketorolac in neonates and infants after cardiac surgery. Paediatr Anaesth. 2006 Apr;16(4):424-8. doi: 10.1111/j.1460-9592.2005.01806.x. — View Citation

Onaka T, Yagi K. Differential effects of naloxone on neuroendocrine responses to fear-related emotional stress. Exp Brain Res. 1990;81(1):53-8. doi: 10.1007/BF00230100. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	1. Total fentanyl dose equivalents received within the first 96 hours post-operatively	The total opioid receipt (converted to fentanyl equivalents) administered to patients enrolled in the study within the first 96 hours after cardiac surgery.	Within 72 hours of cardiac surgery
Secondary	1. Total fentanyl equivalents received in each 24 hour period before and after initiating the study drug	The total opioid receipt (converted to fentanyl equivalents) administered to patients enrolled in the study within each 24 hour period after cardiac surgery (up to 96 hours post-operatively).	Within 72 hours after cardiac surgery
Secondary	Rate of acute kidney injury measured by pRIFLE criteria	Acute kidney injury rates	Within 72 hours after cardiac surgery
Secondary	Major bleeding events	Hemoglobin decrease > 2 g/dL, requirement of 2 or more units of PRBC's/whole blood, or development of symptomatic/clinically evident bleeding in any organ or compartment	Within 72 hours after cardiac surgery
Secondary	Pain scores	FLACC scores (face, legs, activity, cry, consolability): score of 0-10 (10 being most severe pain, 0 being least severe). 0 = relaxed/comfortable, 1-3 = mild discomfort, 4-6 = moderate pain, 7-10 = severe discomfort or pain or both	Within 72 hours after cardiac surgery
Secondary	Sedative agent requirements	Dose receipt/drug selection of sedative agents	Within 72 hours after cardiac surgery