Effect of Ketorolac on Post Adenotonsillectomy Pain

Ketorolac as a Strategy for Reducing Post-operative Opioid Requirements in Children With Obstructive Sleep Apnea Undergoing Adenotonsillectomy: a Randomized Controlled Trial

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03467750

Enrollment

Registered

2018-03-16

Start date

2018-07-19

Completion date

2023-08-22

Last updated

2024-09-19

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Obstructive Sleep Apnea

Keywords

Adenotonsillectomy, Opioids, Post-surgical pain, Anesthesiology, Pediatrics

Brief summary

This randomized prospective study aims to determine the effect of ketorolac on the total dose of morphine required to achieve postoperative analgesia in children with obstructive sleep apnea (OSA) undergoing adenotonsillectomy. Participants will be randomly assigned to a study group where they will receive ketorolac in addition to the standard of care treatment or will receive only the standard of care pain management. The researchers hypothesize that by administering ketorolac at the end of the procedure once hemostasis has been achieved, it will be possible to decrease the amount of morphine administered in the post-anesthesia care unit (PACU). This study aims to provide a more comprehensive understanding of the efficacy and safety of the current standard post-operative analgesic regimen employed at the study institution, in which opioid analgesia currently plays a prominent role.

Detailed description

Obstructive sleep apnea (OSA) as an indication for adenotonsillectomy has increased significantly over the past ten years, and now has surpassed recurrent tonsillitis as the most common indication for this procedure. Opioids continue to be the most commonly administered pain medication for these procedures. Studies have shown that patients with OSA have significantly increased sensitivity to opioids that results in post-operative respiratory depression and apnea when administered via standard opioid dosing protocols. Children with OSA were shown to have a nearly fivefold increase in the odds of developing respiratory complications when compared to their counterparts with tonsillitis. Ketorolac possesses similar efficacy to morphine without the problematic complications of respiratory depression, nausea and vomiting, which are commonly seen post-adenotonsillectomy. Importantly, when combined with opioids, ketorolac is opioid-sparing. This synergistic effect means that a similar level of analgesia is achieved using a lower dose of opioid. However, there continues to be concern about using ketorolac due to the potential risk of post-operative bleeding from anti-platelet activity. This randomized, prospective study aims to determine the effect of ketorolac on the total dose of morphine required to achieve postoperative analgesia in children with OSA undergoing adenotonsillectomy. Participants will be randomly assigned to receive ketorolac or to not receive ketorolac. The post-anesthesia care unit (PACU) nurses, who will be blinded to ketorolac administration, will evaluate the patients using the Face, Legs, Activity, Cry, Consolability (FLACC) scale scores at 10 minutes post-op, 20 minutes post-op and at time of PACU discharge. For patients with a FLACC score of 6-10, morphine (0.05mg/kg) will be administered. For patients with FLACC scores of 3-5, morphine (0.025mg/kg) will be administered. The total amount of opioid required to obtain a FLACC score of less than 3 will be evaluated as the primary outcome. The secondary outcomes to be evaluated will be PACU FLACC scores, time required in PACU, incidence of post-tonsillectomy bleeding and total pain medications administered during hospital admission.

Interventions

DRUGKetorolac

Patients in this group will receive 0.5mg/kg of ketorolac, administered intravenously.

DRUGStandard of Care

All patients will undergo inhalational induction with nitrous oxide and sevoflurane. After intravenous (IV) placement, 1-3mg/kg of propofol and 1mcg/kg of fentanyl will be administered. After induction, 0.5mg/kg of dexamethasone and an IV infusion of 15mg/kg of acetaminophen will be administered. During surgery, 0.5mcg/kg of dexmedetomidine and 0.1mg/kg ondansetron will be given. A rescue dose of 0.5-1mcg/kg of IV Fentanyl will be available for use at the end of the procedure. The decision to administer will be left to the discretion of the attending anesthesiologist. The choice to give this will be made based on variables including patient's condition and a 20% increase in the heart rate and blood pressure. The PACU nurses, who will be blinded to ketorolac administration, will evaluate the patients using FLACC scores. For patients with a FLACC score of 6-10, morphine 0.05mg/kg will be administered. For patients with FLACC scores of 3-5, morphine 0.025mg/kg will be administered.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

SUPPORTIVE_CARE

Masking

SINGLE (Caregiver)

Masking description

The PACU nurses will be blinded to ketorolac administration, but will be informed of all other medications given. The PACU nurses will evaluate the patients using FLACC scores at 10 minutes post-op, 20 minutes post-op and at time of PACU discharge. Morphine will be administered to obtain a FLACC score of less than 3.

Eligibility

Sex/Gender

ALL

Age

2 Years to 18 Years

Healthy volunteers

Inclusion criteria

* Diagnosis of sleep disordered breathing or obstructive sleep apnea * Children undergoing elective tonsillectomy or adenotonsillectomy at Children's Healthcare of Atlanta Egleston location * Parent or legal guardian willing to participate, and able to understand and sign the provided informed consent

Exclusion criteria

* Known coagulation defect * Patients on longstanding NSAID therapy * Known renal impairment

Design outcomes

Primary

Measure	Time frame	Description
Post-Anesthesia Care Unit (PACU) Morphine Requirements	Until PACU discharge (up to 261 minutes)	The total postoperative morphine dosage required to achieve analgesia (defined as a Face, Legs, Activity, Cry, Consolability (FLACC) Scale score of less than 3) in children with obstructive sleep apnea undergoing adenotonsillectomy was compared between study arms to examine the effect of ketorolac administration.

Secondary

Measure	Time frame	Description
Face, Legs, Activity, Cry, Consolability (FLACC) Scale Score	10 minutes post-op, 20 minutes post-op, PACU discharge (up to 261 minutes)	Post-Anesthesia Care Unit (PACU) nurses evaluated the patients using Face, Legs, Activity, Cry, Consolability (FLACC) Scale scores at 10 minutes post-op, 20 minutes post-op and at time of PACU discharge. Each category is scored as 0 (no indication of pain), 1 (indication of moderate pain), or 2 (visibly experiencing severe pain). Total scores range from 0 to 10, with higher scores indicating more pain.
Post-Anesthesia Care Unit (PACU) Recovery Time	Until PACU discharge (up to 261 minutes)	The duration of time that a participant was in the Post-Anesthesia Care Unit (PACU), following surgery, measured in minutes.
Number of Participants With Post-Tonsillectomy Bleeding	Up to 14 days after surgery	Participants were monitored via medical chart review for post-tonsillectomy bleeding.
Pain Medication Administration	Surgery through hospital discharge (up to post-operative day 2)	The total amount of pain medications administered during hospitalization was examined.

Countries

United States

Participant flow

Recruitment details

Participants were recruited from Children's Healthcare of Atlanta at Egleston in Atlanta, Georgia, USA. Participant enrollment began July 19, 2018 and the final study assessment occurred on August 22, 2023.

Participants by arm

Arm	Count
Ketorolac Participants randomized to the ketorolac group received 0.5mg/kg IV at the end of the adenotonsillectomy procedure, once hemostasis was achieved.	30
Standard of Care Participants randomized to this group received the pain management standard of care for the adenotonsillectomy procedure.	33
Total	63

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Protocol Violation	1	1
Overall Study	Surgery canceled	1	0
Overall Study	Withdrawal by Subject	0	1

Baseline characteristics

Characteristic	Ketorolac	Total	Standard of Care
Age, Continuous	4.43 years STANDARD_DEVIATION 3.2	4.40 years STANDARD_DEVIATION 3.03	4.36 years STANDARD_DEVIATION 2.91
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) Black or African American	14 Participants	34 Participants	20 Participants
Race (NIH/OMB) More than one race	0 Participants	2 Participants	2 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	16 Participants	26 Participants	10 Participants
Region of Enrollment United States	30 participants	63 participants	33 participants
Sex: Female, Male Female	11 Participants	30 Participants	19 Participants
Sex: Female, Male Male	19 Participants	33 Participants	14 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 29	0 / 32
other Total, other adverse events	1 / 29	2 / 32
serious Total, serious adverse events	0 / 29	0 / 32

Outcome results

Primary

Post-Anesthesia Care Unit (PACU) Morphine Requirements

The total postoperative morphine dosage required to achieve analgesia (defined as a Face, Legs, Activity, Cry, Consolability (FLACC) Scale score of less than 3) in children with obstructive sleep apnea undergoing adenotonsillectomy was compared between study arms to examine the effect of ketorolac administration.

Time frame: Until PACU discharge (up to 261 minutes)