Ketorolac on Postoperative Pain Reduction in Pediatric Patients with Adenotonsillectomy

NCT ID: NCT05074056

Last Updated: 2025-02-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 142 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-02-08
• Study Completion Date: 2024-12-30

Brief Summary

Postoperative pain management in the pediatric patient undergoing 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 showed that only 8.2% of anesthesiologists use NSAIDS for perioperative management of children with OSA undergoing adenotonsillectomy. The investigators propose to conduct a prospective, randomized study to investigate the opioid-sparing effect of perioperative ketorolac in pediatric patients who undergo tonsillectomies.

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 recurrent 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 undergoing tonsillectomies and postoperative pain is also correlated with emergence agitation, ileus, delayed mobilization, prolonged hospital stays, the development of chronic pain syndromes, and 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 the incidence of PONV, and cutting down clinical symptoms related to opioid overdose.

To better control postoperative pain, pre-operative and intraoperative pain management 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 events 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, resulting in desaturation of blood oxygen, and even death. Multi-modal pain control includes use of combinations of opioids with selective alpha2-adrenergic agonist such as dexmedetomidine and nonsteroidal anti-inflammatory drugs (NSAIDS) such as ketorolac, are frequently used for analgesia in children undergoing tonsillectomies. 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. A meta-analysis 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 to support that conclusion.

Despite of these findings, perioperative ketorolac usage, especially in pediatric tonsillectomy surgery, is very limited.

Conditions

Adenotonsillar Hypertrophy; Obstructive Sleep Apnea; Sleep-Disordered Breathing; Acute Post Operative Pain

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Ketorolac

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

Group Type: EXPERIMENTAL

Ketorolac

Intervention Type: DRUG

We will administer intraoperative ketorlac.

Placebo

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

Group Type: PLACEBO_COMPARATOR

Ketorolac

Intervention Type: DRUG

We will administer intraoperative ketorlac.

Interventions

Ketorolac

We will administer intraoperative ketorlac.

Intervention Type: DRUG

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

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

St. Louis University

OTHER

Sponsor Role: lead

Responsible Party

Andrea Zepeda, MD

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

SSM Cardinal Glennon Children's Hospital

St Louis, Missouri, United States

Countries

United States

References

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Other Identifiers

31070

Identifier Type: -

Identifier Source: org_study_id