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Ketorolac on Postoperative Pain Reduction in Pediatric Patients With Adenotonsillectomy

Primary Purpose

Adenotonsillar Hypertrophy, Obstructive Sleep Apnea, Sleep-Disordered Breathing

Status
Recruiting
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Ketorolac
Sponsored by
St. Louis University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adenotonsillar Hypertrophy

Eligibility Criteria

3 Years - 12 Years (Child)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Adenotonsillar hypertrophy
  • ASA II
  • Otherwise healthy child

Exclusion Criteria:

  • Child < 3 years old and > 12 years old
  • Severe Obstructive sleep apnea
  • Chronic Kidney disease
  • Chronic Liver Disease

Sites / Locations

  • SSM Cardinal Glennon Children's HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Ketorolac

Placebo

Arm Description

A double-blinded number of children will get one dose of intravenous 0.5 mg/kg (max dose 30mg) ketorolac intraoperatively.

A double-blinded number of children will get one dose of intravenous placebo intraoperatively.

Outcomes

Primary Outcome Measures

Postoperative pain management
Change in pain score using the Wong-Baker FACES Pain Rating Scale (0-10 scale with 0 being "no hurt" and 10 being "hurts worst") and 0-10 Numeric Pain Intensity Scale (0-10 scale with 0 being "no pain" and 10 being "Worst pain").

Secondary Outcome Measures

Full Information

First Posted
September 29, 2021
Last Updated
February 14, 2023
Sponsor
St. Louis University
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1. Study Identification

Unique Protocol Identification Number
NCT05074056
Brief Title
Ketorolac on Postoperative Pain Reduction in Pediatric Patients With Adenotonsillectomy
Official Title
Evaluation of Perioperative Usage of Ketorolac on Postoperative Pain Reduction in Pediatric Patients With Adenotonsillectom
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 8, 2022 (Actual)
Primary Completion Date
June 30, 2024 (Anticipated)
Study Completion Date
June 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
St. Louis University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Postoperative pain management in pediatric patient with tonsillectomy is challenging. Despite being used in many procedures for postoperative pain management, perioperative ketorolac usage in pediatric tonsillectomy surgery is very limited. A recent survey shows that only 8.2% of anesthesiologists use NSAIDS for perioperative management of children with OSA undergoing adenotonsillectomy. We propose to conduct a perspective, randomized study to investigate the opioid-sparing effect of perioperative ketorolac in pediatric patients who have tonsillectomy.
Detailed Description
Adenotonsillectomy is one of the most frequent surgeries performed in pediatric population in the United States mainly due to conditions such as sleep disordered breathing, and tonsillitis. However, postoperative pain control following adenotonsillectomy still offers great challenges to anesthesiologists. Postoperative pain has been the most common adverse effect in post-anesthesia care unit (PACU) for children after tonsillectomy, and postoperative pain is also correlated with emergence agitation, ileus, delayed mobilization, prolonged hospital stays, the development of chronic pain syndromes, as well as postoperative nausea and vomiting (PONV). Therefore, benefits of effective pain control are many fold: improving patient/family satisfaction, reducing the risk of postoperative bleeding due to emergence agitation, decreasing incidence of PONV, and cutting down clinical symptoms related to opioid overdose. To better control postoperative pain, pre-operative and intraoperative pain managements have been the key. Preventative analgesic interventions may provide protection against the development of persistent postoperative pain. Although opioid derivatives such as fentanyl and morphine are mainstays for the perioperative management of post-tonsillectomy pain, opioid consumption is positively correlated with clinical adverse effects such as PONV, opioid overdose, and over-sedation. Especially for pediatric patients with severe obstructive sleep apnea (OSA), opioids may depress ventilation and lead to further airway obstruction, result in desaturation of blood oxygen, and even death. Multi-modal pain control including using of combinations of opioids with selective alpha2-adrenergic agonist such as dexmedetomidine, nonsteroidal anti-inflammatory drugs (NSAIDS), such as ketorolac, are frequently used for analgesia in children undergoing tonsillectomy. Dexmedetomidine is a selective alpha-2 adrenergic receptor agonist that directly acts on the peripheral nervous system, causing a dose-dependent inhibition of C-fibers and Aα-fibers. Non-selective NSAIDS have been shown to function both peripherally and centrally in nociception. NSAIDs act at the peripheral nociceptors by blocking the cyclooxygenase (COX) enzyme that inhibits the conversion of arachidonic acid to prostaglandins, thereby preventing the sensitization of pain receptors in response to injury. Centrally, NSAIDs inhibit prostaglandin E2 (PGE2) production in the spinal dorsal horn via COX-2, activate medullary and cortical brain regions involved in the descending inhibitory pain cascade, result in central sensitization and a lower pain threshold in the surrounding uninjured tissue. Among NSAIDS, Ketorolac tromethamine (Toradol) is the first approved for parenteral use in 1990 in the United States. Despite its variety of clinical indications, it is mainly administered for the management of postoperative pain It has strong analgesic properties, with a dose of 30 mg intramuscular (IM) offering similar analgesia as 12 mg of morphine. The strong analgesic properties of reducing opioid requirements make it a good candidate in multi-modal pain management of post-tonsillectomy pain. Unlike opioid analgesics, ketorolac does not depress ventilation, and is not associated with nausea and vomiting, urinary retention or sedation. When combined with an opioid, ketorolac exhibits significant opioid-sparing effects, allowing a lower dosage of opioid to be used. Clinical studies in children and adults show that the synergistic action of ketorolac and opioids improves the degree and quality of pain relief, and reduces the incidence of opioid-related adverse effects such as respiratory depression, PONV, and ileus. However, similar to other non-selective Cox enzyme inhibitors, ketorolac has several adverse effects including gastrointestinal (GI) bleeding, renal impairment, liver dysfunction, possible allergic reactions, and disruption of platelet aggregation through the inhibition of thromboxane A. However, the evidence of increased bleeding is conflicting. Philips-Reed et al conducted a metanalysis suggested that there was no consensus on the increased risk of bleeding when NSAIDS such as ketorolac are given to pediatric patients undergoing tonsillectomy. There are other analyses support their conclusion. Despite of these findings, perioperative ketorolac usage, especially in pediatric tonsillectomy surgery, is very limited.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adenotonsillar Hypertrophy, Obstructive Sleep Apnea, Sleep-Disordered Breathing, Acute Post Operative Pain

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
Prospective Randomized Study
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Double Blind
Allocation
Randomized
Enrollment
200 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Ketorolac
Arm Type
Experimental
Arm Description
A double-blinded number of children will get one dose of intravenous 0.5 mg/kg (max dose 30mg) ketorolac intraoperatively.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
A double-blinded number of children will get one dose of intravenous placebo intraoperatively.
Intervention Type
Drug
Intervention Name(s)
Ketorolac
Intervention Description
We will administer intraoperative ketorlac.
Primary Outcome Measure Information:
Title
Postoperative pain management
Description
Change in pain score using the Wong-Baker FACES Pain Rating Scale (0-10 scale with 0 being "no hurt" and 10 being "hurts worst") and 0-10 Numeric Pain Intensity Scale (0-10 scale with 0 being "no pain" and 10 being "Worst pain").
Time Frame
two hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
3 Years
Maximum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Adenotonsillar hypertrophy ASA II Otherwise healthy child Exclusion Criteria: Child < 3 years old and > 12 years old Severe Obstructive sleep apnea Chronic Kidney disease Chronic Liver Disease
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Andrea G Zepeda, M.D.
Phone
314-577-5622
Email
andrea.zepeda@health.slu.com
First Name & Middle Initial & Last Name or Official Title & Degree
Pin Yue, C.A.A.
Phone
314-577-5622
Email
pin.yue@health.slu.edu
Facility Information:
Facility Name
SSM Cardinal Glennon Children's Hospital
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andrea Zepeda, M.D.
Phone
314-678-5130
Email
andrea.zepeda@health.slu.edu
First Name & Middle Initial & Last Name & Degree
Pin Yue, PhD
Phone
3145775622
Email
pin.yue@health.slu.edu

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
31077491
Citation
Franz AM, Dahl JP, Huang H, Verma ST, Martin LD, Martin LD, Low DK. The development of an opioid sparing anesthesia protocol for pediatric ambulatory tonsillectomy and adenotonsillectomy surgery-A quality improvement project. Paediatr Anaesth. 2019 Jul;29(7):682-689. doi: 10.1111/pan.13662. Epub 2019 Jun 19.
Results Reference
background
PubMed Identifier
28662233
Citation
Tan GX, Tunkel DE. Control of Pain After Tonsillectomy in Children: A Review. JAMA Otolaryngol Head Neck Surg. 2017 Sep 1;143(9):937-942. doi: 10.1001/jamaoto.2017.0845.
Results Reference
background
PubMed Identifier
30281185
Citation
Scalzitti NJ, Sarber KM. Diagnosis and perioperative management in pediatric sleep-disordered breathing. Paediatr Anaesth. 2018 Nov;28(11):940-946. doi: 10.1111/pan.13506. Epub 2018 Oct 3.
Results Reference
background
PubMed Identifier
28860845
Citation
Tang C, Xia Z. Dexmedetomidine in perioperative acute pain management: a non-opioid adjuvant analgesic. J Pain Res. 2017 Aug 11;10:1899-1904. doi: 10.2147/JPR.S139387. eCollection 2017.
Results Reference
background
PubMed Identifier
27841015
Citation
Gupta A, Bah M. NSAIDs in the Treatment of Postoperative Pain. Curr Pain Headache Rep. 2016 Nov;20(11):62. doi: 10.1007/s11916-016-0591-7.
Results Reference
background
PubMed Identifier
8922554
Citation
Cashman JN. The mechanisms of action of NSAIDs in analgesia. Drugs. 1996;52 Suppl 5:13-23. doi: 10.2165/00003495-199600525-00004.
Results Reference
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PubMed Identifier
28526155
Citation
Vadivelu N, Chang D, Helander EM, Bordelon GJ, Kai A, Kaye AD, Hsu D, Bang D, Julka I. Ketorolac, Oxymorphone, Tapentadol, and Tramadol: A Comprehensive Review. Anesthesiol Clin. 2017 Jun;35(2):e1-e20. doi: 10.1016/j.anclin.2017.01.001. Epub 2017 Apr 14.
Results Reference
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PubMed Identifier
27440142
Citation
Maslin B, Lipana L, Roth B, Kodumudi G, Vadivelu N. Safety Considerations in the Use of Ketorolac for Postoperative Pain. Curr Drug Saf. 2017;12(1):67-73. doi: 10.2174/1574886311666160719154420.
Results Reference
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PubMed Identifier
9187531
Citation
Forrest JB, Heitlinger EL, Revell S. Ketorolac for postoperative pain management in children. Drug Saf. 1997 May;16(5):309-29. doi: 10.2165/00002018-199716050-00003.
Results Reference
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PubMed Identifier
11883386
Citation
Forrest JB, Camu F, Greer IA, Kehlet H, Abdalla M, Bonnet F, Ebrahim S, Escolar G, Jage J, Pocock S, Velo G, Langman MJ, Bianchi PG, Samama MM, Heitlinger E; POINT Investigators. Ketorolac, diclofenac, and ketoprofen are equally safe for pain relief after major surgery. Br J Anaesth. 2002 Feb;88(2):227-33. doi: 10.1093/bja/88.2.227.
Results Reference
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PubMed Identifier
27931700
Citation
Phillips-Reed LD, Austin PN, Rodriguez RE. Pediatric Tonsillectomy and Ketorolac. J Perianesth Nurs. 2016 Dec;31(6):485-494. doi: 10.1016/j.jopan.2015.02.005. Epub 2016 May 5.
Results Reference
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PubMed Identifier
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Citation
Lewis SR, Nicholson A, Cardwell ME, Siviter G, Smith AF. Nonsteroidal anti-inflammatory drugs and perioperative bleeding in paediatric tonsillectomy. Cochrane Database Syst Rev. 2013 Jul 18;2013(7):CD003591. doi: 10.1002/14651858.CD003591.pub3.
Results Reference
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Citation
Roberts C, Al Sayegh R, Ellison PR, Sedeek K, Carr MM. How Pediatric Anesthesiologists Manage Children with OSA Undergoing Tonsillectomy. Ann Otol Rhinol Laryngol. 2020 Jan;129(1):55-62. doi: 10.1177/0003489419874371. Epub 2019 Sep 5.
Results Reference
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Ketorolac on Postoperative Pain Reduction in Pediatric Patients With Adenotonsillectomy

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