TerminatedNCT01737593Updated Oct 21, 2016Results posted

Can Acetaminophen Given 1-2 Hours to Children Before Ear Tube Surgery Reduce Agitation After Anesthesia?

A Phase 4 interventional study of Acetaminophen in Emergence Agitation and Pain, sponsored by University of California, Los Angeles. Terminated at 1 site in United States. Open to participants aged 6 Months to 6 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2016-10-21.

Sponsored by University of California, Los Angeles · Phase 4, Interventional, and Supportive care

Why this study was terminated

Interim analysis revealed a negative effect.

Phase: Phase 4
Study type: Interventional
Enrollment: 108
Allocation: Randomized
Ages: 6 Months to 6 Years
Sex: All

Study summary

Emergence agitation (EA) occurs in up to 67% of pediatric patients after anesthesia for bilateral myringotomy tubes (BMT, "ear tubes"). The goal of this study is to find out whether acetaminophen given well before surgery can decrease pain and therefore, decrease emergence agitation better than acetaminophen given shortly before or during surgery. EA can be dangerous for the patient because it may be hard to monitor their vital signs during an important phase of recovery, they may injure themselves, may require the presence of extra staff, and it can be very distressing to the parents. Causes of EA are not well understood, but it can be worsened by pain. 70% of patients undergoing BMT experience pain that needs treatment. Intranasal fentanyl, a strong analgesic, has been shown to decrease EA, but often ends up in dose-dependent nausea and vomiting. In previous studies and in common practice, acetaminophen is given either 30 minutes before induction of anesthesia or immediately after induction. The peak analgesic effect of acetaminophen is 60-120 minutes. Since the procedure is generally completed in 5-10 minutes, the therapeutic effect of acetaminophen may not be present upon emergence from anesthesia.

The purpose of this study is to find out if acetaminophen given 60-120 minutes prior to emergence can decrease EA in patients undergoing BMT. Patients would be randomized to one of three groups: Control will receive acetaminophen rectally while under anesthesia (standard practice), Group 1 will receive acetaminophen 10 mg/kg at 60-120 minutes prior to surgery, Group 2 will receive acetaminophen 20 mg/kg at 60-120 minutes prior to surgery. All groups would also receive a dose of intranasal fentanyl during the surgery, which is standard practice. Patients would be observed in the recovery room at various time points for evidence of EA and pain.

Read the detailed description

Emergence agitation (EA) occurs in up to 67% of patients undergoing Sevoflurane anesthesia for bilateral myringotomy tube placement (BMT). Often EA presents as inconsolable screaming, crying, thrashing, and kicking, and may require restraints. It can be dangerous for the patient because it may be difficult to monitor their vital signs during a critical phase of recovery (i.e. unable to detect hypoxemia), they may injure themselves as they thrash about, it usually requires the presence of extra staff, and it can be very distressing to the parents. Causes of EA are theoretical, but can be exacerbated by pain. 70% of patients undergoing BMT have pain requiring treatment. Since BMT is performed without IV placement the options for analgesia are limited to intranasal fentanyl, intramuscular ketorolac, rectal or oral acetaminophen, oral opioids (i.e. codeine, oxycodone). Intranasal Fentanyl has been shown to decrease EA, but results in post operative nausea and vomiting, as with any opioids. Intramuscular ketorolac is costly and can lead to hematomas. In previous studies (common practice), acetaminophen is given either 30 minutes before induction (PO route) or immediately after induction (PR route). Since the procedure is generally completed in 5-10 minutes, the therapeutic effect of acetaminophen can not be appreciated. The peak effect (for analgesia) of acetaminophen is 60-120 minutes. Our hypothesis: If acetaminophen is given 60-120 minutes prior to emergence, when it reaches therapeutic effect, it can decrease EA in patients undergoing BMT. The importance of mitigating EA not only involves patient safety and satisfaction, but will also impact hospital/surgery center efficiency (RN staffing and smoother and shorter recovery periods).

This study will be a randomized controlled trial. Potential subjects will be identified and recruited by study personnel and/or patient's surgeon. Children scheduled for BMT placement whose parents' consent to participate will be enrolled in the study. These patients will be consented on the day of surgery. Parents will be informed that whether they enroll their children in the study or not, they will be receiving standard clinical care. Only subjects meeting all inclusion criteria and requirements for continuation in the study will be consented.

Patients will be enrolled into one of three study groups. All patients meeting all inclusion criteria and requirements for the study (see below) will be identified, consented then computer randomized into either control, group 1 or 2.

Control - acetaminophen PR (20-40mg/kg) after induction of Anesthesia (acetaminophen is in suppository form and given rectally) Group 1 - acetaminophen PO (10mg/kg) 60-120min before start of BMT placement (acetaminophen is in syrup form and given by mouth) Group 2 - acetaminophen PO (20mg/kg) 60-120min before start of BMT placement (acetaminophen is in syrup form and given by mouth)

After randomization, treating physicians will be made aware of what treatment group the patient is assigned to. The data collection and behavior/pain assessments will be made by blinded study personnel in the operating room (only for induction) and PACU.

Data Collection: Data will be collected at the time points: Induction, Emergence (spontaneous extremity movement), and every 5 minutes after emergence until the patient is discharged. There will also be a follow-up questionnaire for the parent on satisfaction with the child's emergence, side effects, additional medications, and his/her PACU experience. This will be conducted on the phone within 36 hours after the parents have left the hospital.

Conditions studied

Emergence Agitation
Pain

Browse trials for

Keywords

acetaminophen
emergence agitation
children
sevoflurane

In context

Psychomotor Agitation

500 studies on the registry are indexed under Psychomotor Agitation; 55 are open to participants now.

This study's enrollment of 108 is above the median of 90 across 413 interventional studies indexed under Psychomotor Agitation.

Browse Psychomotor Agitation studies →

Lead sponsor

University of California, Los Angeles is the lead sponsor of 1,142 studies on the registry; 192 are open to participants now.

Of its 91 completed or terminated interventional studies of FDA-regulated products, 66 (73%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 6 Months to 6 Years
Sexes eligible: All
Accepts healthy volunteers: Yes

Inclusion criteria

Patients' ≥ 6 months - 6 years
Patients must meet criteria for American Society of Anesthesiologists (ASA) physical status I, II.
Patients must not be pre-medicated.
Parents must give written consent on the surgery day and be able to sign informed consent form on the surgery day.
Undergoing BMT surgery only.

Exclusion criteria

Exclusion Criteria:

Patients' \<6 months and >6 years.
Patients with known allergies to any of the medications used in this study.
Patients with ASA status III \& IV.
Patients taking prescription pain medications prior to surgery.
Patients taking medication that can cause drowsiness or alter mental status (eg. benzodiazepines, cough suppressants, diphenhydramine)
Patients with significant history of psychiatric illness, neurologic disease (seizure disorder requiring medication therapy), and developmental delay.
Patients have been pre-medicated.
Patients undergoing other procedures that would prolong anesthetic exposure or confound post-operative pain.
Intra-op complication that would require prolonged anesthetic exposure.
If patient took acetaminophen prior to surgery and was not supposed to do so
Patients that received ketorolac or additional analgesia during surgery.
Patients that have liver disease.

Study design

Phase: Phase 4
Primary purpose: Supportive care
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Double (Participant, Outcomes assessor)
Enrollment: 108 participants (actual)

Study arms

Active comparator
Acetaminophen PR
Acetaminophen PR (20-40mg/kg) after induction of Anesthesia (acetaminophen is in suppository form and given rectally)
Drug: Acetaminophen
Active comparator
Acetaminophen PO-low dose
Acetaminophen PO (10mg/kg) 60-120min before start of BMT placement (acetaminophen is in syrup form and given by mouth)
Drug: Acetaminophen
Active comparator
Acetaminophen PO-high dose
Acetaminophen PO (20mg/kg) 60-120min before start of BMT placement (acetaminophen is in syrup form and given by mouth)
Drug: Acetaminophen

Interventions

DrugAcetaminophen
Also known as: Tylenol

What researchers measure

Primary outcomes

Postanesthesia Emergence Agitation (EA) Score
EA was evaluated using the Pediatric Anesthesia Emergence Delirium (PAED) scale. This scale measures if the: 1. Child makes eye contact with the caregiver, 2. Child's actions are purposeful, 3. Child is aware of his/her surroundings, 4. Child is restless, 5. Child is inconsolable. Items 1, 2, and 3 are reversed scored as follows: 4 _ not at all, 3 _ just a little, 2 _ quite a bit, 1 _ very much, 0 _ extremely. Items 4 and 5 are scored as follows: 0 _ not at all, 1 _ just a little, 2 _ quite a bit, 3 _ very much, 4_extremely. Scores of each item are summed to obtain a total PAED scale score, range 0-20, with higher PAED scores indicating a greater degree of emergence delirium. The average PAED score of all the time points is use
Time frame: Induction,Emergence(spontaneous extremity movement),and every 5 min after emergence until the patient is discharged. This is an average of 3 hours till discharge.

Secondary outcomes

Postanesthesia Pain Score
Children's Hospital of Eastern Ontario pain scale (CHEOPS) is an observational scale for measuring postoperative pain in young children. The scale includes six categories of pain behavior: (Cry, facial, verbal, torso, touch, and legs). A score ranging from 0 to 2 or 1 to 3 is assigned to each activity and the summed score ranges between 4 and 13, with a higher score meaning more pain.
Time frame: Induction
Postanesthesia Pain Score
Children's Hospital of Eastern Ontario pain scale (CHEOPS) is an observational scale for measuring postoperative pain in young children. The scale includes six categories of pain behavior: (Cry, facial, verbal, torso, touch, and legs). A score ranging from 0 to 2 or 1 to 3 is assigned to each activity and the summed score ranges between 4 and 13, with a higher score meaning more pain.
Time frame: Emergence (spontaneous extremity movement)
Postanesthesia Pain Score
Children's Hospital of Eastern Ontario pain scale (CHEOPS) is an observational scale for measuring postoperative pain in young children. The scale includes six categories of pain behavior: (Cry, facial, verbal, torso, touch, and legs). A score ranging from 0 to 2 or 1 to 3 is assigned to each activity and the summed score ranges between 4 and 13, with a higher score meaning more pain.
Time frame: 5 minutes post-emergence
Postanesthesia Pain Score
Children's Hospital of Eastern Ontario pain scale (CHEOPS) is an observational scale for measuring postoperative pain in young children. The scale includes six categories of pain behavior: (Cry, facial, verbal, torso, touch, and legs). A score ranging from 0 to 2 or 1 to 3 is assigned to each activity and the summed score ranges between 4 and 13, with a higher score meaning more pain.
Time frame: 15 minutes post-emergence
Postanesthesia Pain Score
Children's Hospital of Eastern Ontario pain scale (CHEOPS) is an observational scale for measuring postoperative pain in young children. The scale includes six categories of pain behavior: (Cry, facial, verbal, torso, touch, and legs). A score ranging from 0 to 2 or 1 to 3 is assigned to each activity and the summed score ranges between 4 and 13, with a higher score meaning more pain.
Time frame: 30 minutes post-emergence
Postanesthesia Pain Score
Children's Hospital of Eastern Ontario pain scale (CHEOPS) is an observational scale for measuring postoperative pain in young children. The scale includes six categories of pain behavior: (Cry, facial, verbal, torso, touch, and legs). A score ranging from 0 to 2 or 1 to 3 is assigned to each activity and the summed score ranges between 4 and 13, with a higher score meaning more pain.
Time frame: 45 minutes post-emergence
Postanesthesia Pain Score
Children's Hospital of Eastern Ontario pain scale (CHEOPS) is an observational scale for measuring postoperative pain in young children. The scale includes six categories of pain behavior: (Cry, facial, verbal, torso, touch, and legs). A score ranging from 0 to 2 or 1 to 3 is assigned to each activity and the summed score ranges between 4 and 13, with a higher score meaning more pain.
Time frame: Prior to discharge, up to 3 hours after induction.

Results

Posted Oct 21, 2016

Participant flow

Participant flow — Overall Study
Milestone	Acetaminophen PR	Acetaminophen PO-low Dose	Acetaminophen PO-high Dose
Started	37	32	39
Completed	37	32	39
Not completed	0	0	0

Outcome measures

PrimaryPostanesthesia Emergence Agitation (EA) Score

EA was evaluated using the Pediatric Anesthesia Emergence Delirium (PAED) scale. This scale measures if the: 1. Child makes eye contact with the caregiver, 2. Child's actions are purposeful, 3. Child is aware of his/her surroundings, 4. Child is restless, 5. Child is inconsolable. Items 1, 2, and 3 are reversed scored as follows: 4 _ not at all, 3 _ just a little, 2 _ quite a bit, 1 _ very much, 0 _ extremely. Items 4 and 5 are scored as follows: 0 _ not at all, 1 _ just a little, 2 _ quite a bit, 3 _ very much, 4_extremely. Scores of each item are summed to obtain a total PAED scale score, range 0-20, with higher PAED scores indicating a greater degree of emergence delirium. The average PAED score of all the time points is use

Time frame:: Induction,Emergence(spontaneous extremity movement),and every 5 min after emergence until the patient is discharged. This is an average of 3 hours till discharge.
Reported as:: Mean · units on a scale

Postanesthesia Emergence Agitation (EA) Score
units on a scale	Acetaminophen by Rectum (PR)	Acetaminophen by Mouth (PO) - Low Dose	Acetaminophen by Mouth (PO) - High Dose
Postanesthesia Emergence Agitation (EA) Score	5.63 ± 3.07	6.19 ± 3.53	6.37 ± 3.96