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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment | Experimental |
|
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| Standard of care | Placebo Comparator |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Continuous ketorolac | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Kevin Engelhardt, MD | Contact | 6029333366 | kengelhardt@phoenixchildrens.com | |
| Samantha Stack, BS | Contact | 6029330607 | sstack@phoenixchildrens.com |
| Name | Affiliation | Role |
|---|---|---|
| Kevin Engelhardt, MD | Heart Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Phoenix Children's Hospital | Recruiting | Phoenix | Arizona | 85016 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 2168320 | Background | 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. | |
| 11902701 | Background | Burd RS, Tobias JD. Ketorolac for pain management after abdominal surgical procedures in infants. South Med J. 2002 Mar;95(3):331-3. |
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We do not plan to make IPD available to other researchers.
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| ID | Term |
|---|---|
| D000377 | Agnosia |
| D006330 | Heart Defects, Congenital |
| ID | Term |
|---|---|
| D010468 | Perceptual Disorders |
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
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Randomized, placebo-controlled
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Double-blind
| Rate of acute kidney injury measured by pRIFLE criteria |
Acute kidney injury rates |
| Within 72 hours after cardiac surgery |
| 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 |
| 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 |
| Sedative agent requirements | Dose receipt/drug selection of sedative agents | Within 72 hours after cardiac surgery |
| 1911008 | Background | 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. |
| 21233498 | Background | 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. |
| 19134246 | Background | 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. |
| 23058854 | Background | 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. |
| 15365927 | Background | 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. |
| 27580638 | Background | 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. |
| 8970395 | Background | 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. |
| 19562323 | Background | 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. |
| 24441450 | Background | 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. |
| 16618297 | Background | 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. |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D018376 | Cardiovascular Abnormalities |
| D002318 | Cardiovascular Diseases |
| D006331 | Heart Diseases |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |