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CompletedNCT00468052Updated Dec 5, 2016Results posted

Decrease Emergence Agitation and Provide Pain Relief for Children Undergoing Tonsillectomy & Adenoidectomy

A Phase 3 interventional study of dexmedetomidine and fentanyl in Obstructive Sleep Apnea, sponsored by University of Medicine and Dentistry of New Jersey. Completed at 1 site in United States. Open to participants aged 2 Years to 10 Years. Per ClinicalTrials.gov, last updated 2016-12-05.

Sponsored by University of Medicine and Dentistry of New Jersey · Phase 3, Interventional, and Prevention

Phase
Phase 3
Study type
Interventional
Enrollment
122
Allocation
Randomized
Ages
2 Years to 10 Years
Sex
All
01

Study summary

Pediatric tonsillectomy (with or without adenoidectomy) is a brief but painful surgery carried out in children who very often also present with obstructive sleep apnea. To provide pain relief, i.e. analgesia, current practice relies on opioids , e.g., morphine or fentanyl. These narcotics are known to depress respiration and to increase the incidence of post-operative nausea and vomiting. These side effects are worrisome in this patient cohort. An alternative medication, dexmedetomidine, may have an opiate sparing effect and has a high safety profile in adults as well as in sedation in children. The purpose of this study is to determine if intravenous dexmedetomidine given as an infusion during general anesthesia for tonsillectomy or adenotonsillectomy reduces the incidence and severity of emergence agitation, improves analgesia and reduces nausea and vomiting in the 60 minutes following surgery.

Read the detailed description

Emergence agitation (EA) from general anesthesia is a frequent phenomenon in children age 1-10 yrs recovering from anesthesia that demands increasing nursing care in the PACU, delays reunion with parents and often causes dissatisfaction for parents, and may lead to adverse sequelae in some cases such as physical harm to the child, in particular to the site of surgery (1). Emergence agitation is a state of non purposeful restlessness an inconsolability. This state is often accompanied by thrashing, screaming, prolonged crying and disorientation. Children are generally unaware of their surroundings and cannot be consoled by the caregivers/parents. It is very disturbing for parents to observe this behavior in their children. It is also a safety issue for children and staff. These negative effects of EA have motivated clinicians to investigate possible etiologies and potential treatments for EA.

EA may be in part due to the relative paucity of inhibitory neurotransmitters in children's central nervous system (CNS). As well, all modern anesthetics have been designed to be rapidly eliminated resulting in abrupt change from a state of anesthesia to a state of responsiveness. The result is a difficult problem managing these patients over a 30-50 minute period following pediatric anesthesia.

We propose studying patients scheduled for tonsillectomy or adenotonsillectomy. Adenotonsillar hypertrophy may produce upper airway obstruction, dysphagia, dental malocclusion, altered orofacial growth, altered eustachian tube function, or pulmonary hypertension with cor pulmonale. Obstructive sleep apnea (OSA) is associated with loud snoring during sleep with periods of respiratory pauses terminated with gasping and agitated arousal and has been suggested to have developmental consequences including ADHD, failure to thrive, and nocturnal enuresis (2). Obstructive sleep apnea syndrome is most commonly associated with adenotonsillar hypertrophy and more children are now presenting for adenotonsillectomy (3). Tonsillectomy and adenotonsillectomy are highly successful in eliminating OSA in children and is considered first-line therapy if the family is amenable and there are no specific contraindications, and is approximately 85-95% effective in eliminating OSA in children (4). All children undergoing tonsillectomy or adenoidectomy should be considered to be at increased risk for perioperative airway problems (5). Opioids may cause respiratory depression, and thus present an added risk in patients undergoing tonsillectomy and adenotonsillectomy, especially in children with OSA (6).

The purpose of this study is to determine if intravenous dexmedetomidine given as an infusion during general anesthesia for tonsillectomy or adenotonsillectomy reduces the incidence and severity of emergence agitation in the 60 minutes following surgery compared to normal practice. A second outcome is whether the need for intra-operative and postoperative analgesic narcotic medications is reduced.

Dexmedetomidine, a specific alpha 2-adrenergic receptor agonist, has recently been studied for its sedative, amnestic, and analgesic properties and has been shown to be effective in providing sedation, decreased anesthetic requirements during surgery and in postanesthesia care units, and reduction in emergence agitation (7, 8, 9). Dexmedetomidine has been shown to enhance the analgesic action of nitrous oxide and furthermore it has also been shown to be effective as a total intravenous anesthetic agent in certain patients if doses are increased to a high enough level, with no respiratory depression (10, 11). If dexmedetomidine can be shown to reduce or eliminate emergence agitation, and provide effective intraoperative and postoperative analgesia without respiratory depression, this would give anesthesiologists a better option in the management of patients undergoing tonsillectomy and adenotonsillectomy.

The dosing regimen for Dexmedetomidine in a loading dose of 1ug/kg with with a continuous infusion of 0.2-0.7 ug/kg is recommended for sedation in the Intensive Care Unit for adults. There is an increasing body of experience with use of Dexmedetomidine in pediatrics both for sedation and to reduce kg/hr. They observed a mean decline in heart rate (HR) and blood pressure (BP) from pre-sedation values of 15%, with 70% of patients showing a decline between 1-30%. Despite the drop in HR and BP, all changes were still within the clinical range of normal for age (10). We are proposing 2 ug/kg as a loading dose with a maintenance dose of 0.7ug/kg/hr during surgery, since we intend to use dexmedetomidine during tonsillectomy and adenotonsillectomy, a surgery which can stimulate a pain response and the surgery starts soon after the patient is intubated with no surgical preparation time . 2ug/kg is higher than the usual recommended dose, but has been used in children in the above study without any significant adverse events.

02

Conditions studied

  • Obstructive Sleep Apnea

Keywords

  • obstructive sleep apnea
  • tonsillectomy
  • adenoidectomy
03

In context

Sleep Apnea Syndromes

2,162 studies on the registry are indexed under Sleep Apnea Syndromes; 290 are open to participants now.

This study's enrollment of 122 is above the median of 53 across 1,386 interventional studies indexed under Sleep Apnea Syndromes.

Browse Sleep Apnea Syndromes studies →

Lead sponsor

University of Medicine and Dentistry of New Jersey is the lead sponsor of 103 studies on the registry; none are open to participants now.

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

04

Who can participate

Ages eligible
2 Years to 10 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • ages 2-10 ASA rating of I-III undergoing general anesthesia tonsillectomy with and without adenoidectomy

Exclusion criteria

Exclusion Criteria:

  • diagnosis of anxiety disorder or chronic pain syndrome chronic disabilities or developmental delays are currently on psychotherapeutic or sedating medication are on chronic pain medication or opiate any known adverse effect to the study drug any known cardiac abnormalities
05

Study design

Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Single (Participant)
Enrollment
122 participants (actual)

Study arms

  • Active comparator
    fentanyl

    fentanyl bolus 1ug.kg-1

    Drug: fentanyl

  • Experimental
    dexmedetomidine

    dexmedetomidine 2ug.kg-1 over 10 min followed by 0.7ug.kg-1.h-1

    Drug: dexmedetomidine

Interventions

  • Drugdexmedetomidine

    2 micrograms/kilogram as a bolus then 0.7 micrograms/kilogram infusion

    Also known as: Precedex

  • Drugfentanyl

    1 microgram/kilogram as a bolus

    Also known as: Sublimaze

06

What researchers measure

Primary outcomes

  1. Emergence Agitation and Pain

    emergence agitation and pain will be assessed. Pediatric Anesthesia Emergence Delirium Scale (PAED) range 0-20 a lower score indicates the child is calm and the higher score indicates severe agitation. Cole Agitation Scale was employed which is a 5 point Likert scale. Parameters ranging 1 to 5 1=child is calm and 5 =the child is severly agitated . Objective Pain Score range is 0-10 (higher score the greater pain). 3 Parameters are captured systolic b/p,crying, movements, agitation , complaints of pain

    Time frame: On arrival to PACU and 2 hours postoperatively

  2. Duration of Agitation

    Cole EA scale 1=calm , 5=unconsolable

    Time frame: on arrival to PACU and for 2 hours postoperatively

Secondary outcomes

  1. Hemodynamic Stability

    Participants whose heart rate per minute was below 60 intraoperatively. Participants whose systolic blood pressure dremonstrated \< 30% decrease from baseline and sustained for 5 minutes received rescue as defined by the protocol.

    Time frame: intraoperatively

  2. Time to Awaken

    defined as spontaneous eye opening or on command

    Time frame: at end of surgery

  3. Time to Extubation

    defined as time from end of surgery to tracheal extubation

    Time frame: at end of surgical procedure

  4. Number of Participants With SpO2 < or Equal to 95%

    Time frame: on arrival to PACU and 2 hours postoperatively

  5. Participants Requiring Morphine Rescue in PACU

    Time frame: arrival in PACU to 2 hours postoperatively

07

Results

Posted Oct 11, 2016

Participant flow

Recruitment period April 2007 to June 2009.Children recruited from the practice of the same pediatric otolaryngologist at UH in Newark. The study was introduced to the parent/legal guardian during the preoperative visit. Consent was obtained on the morning of surgery by a member of the pediatric anesthesiology study team.

Participant flow — Overall Study
MilestoneFentanyl (F) GroupDexmedetomidine
Started6869
Target enrollment7070
Completed6161
Not completed78
Withdrew: Protocol violation78

Outcome measures

PrimaryEmergence Agitation and Pain

emergence agitation and pain will be assessed. Pediatric Anesthesia Emergence Delirium Scale (PAED) range 0-20 a lower score indicates the child is calm and the higher score indicates severe agitation. Cole Agitation Scale was employed which is a 5 point Likert scale. Parameters ranging 1 to 5 1=child is calm and 5 =the child is severly agitated . Objective Pain Score range is 0-10 (higher score the greater pain). 3 Parameters are captured systolic b/p,crying, movements, agitation , complaints of pain

Time frame:
On arrival to PACU and 2 hours postoperatively
Reported as:
Median · units on a scale
Emergence Agitation and Pain
units on a scaleFentanyl (F) GroupDexmedetomidine
PAED14 (0 to 20)10 (0 to 20)
Cole EA4 (1 to 5)3 (1 to 5)
OPS5 (0 to 10)3 (0 to 10)
Statistical analysis
  • Fentanyl (F) Group vs Dexmedetomidine · Wilcoxon (Mann-Whitney) · p = .001 (Null hypothesis is not significantly different from group D and F.)
  • Dexmedetomidine · Wilcoxon (Mann-Whitney) · p = .001
PrimaryDuration of Agitation

Cole EA scale 1=calm , 5=unconsolable

Time frame:
on arrival to PACU and for 2 hours postoperatively
Reported as:
Mean · minutes
Duration of Agitation
minutesFentanylDexmedetomidine
Duration of Agitation11.85 ± 12.026.59 ± 7.42
Statistical analysis
  • Fentanyl vs Dexmedetomidine · Wilcoxon (Mann-Whitney) · p = 0.004
SecondaryHemodynamic Stability

Participants whose heart rate per minute was below 60 intraoperatively. Participants whose systolic blood pressure dremonstrated \< 30% decrease from baseline and sustained for 5 minutes received rescue as defined by the protocol.

Time frame:
intraoperatively
Reported as:
Number · participants
Hemodynamic Stability
participantsFentanyl (F) GroupDexmedetomidine
heart rate below 60 bpm00
systolic blood pressure <30% below baseline00
SecondaryTime to Awaken

defined as spontaneous eye opening or on command

Time frame:
at end of surgery
Reported as:
Mean · minutes
Time to Awaken
minutesFentanyl (F) GroupDexmedetomidine
Time to Awaken8.75 ± 4.067.18 ± 4.05
Statistical analysis
  • Fentanyl (F) Group vs Dexmedetomidine · Fisher Exact · p = 0.03
SecondaryTime to Extubation

defined as time from end of surgery to tracheal extubation

Time frame:
at end of surgical procedure
Reported as:
Mean · minutes
Time to Extubation
minutesFentanyl (F) GroupDexmedetomidine
Time to Extubation10.44 ± 4.158.59 ± 4.51
Statistical analysis
  • Fentanyl (F) Group vs Dexmedetomidine · Fisher Exact · p = 0.02
SecondaryNumber of Participants With SpO2 < or Equal to 95%
Time frame:
on arrival to PACU and 2 hours postoperatively
Reported as:
Number · participants
Number of Participants With SpO2 < or Equal to 95%
participantsFentanylDexmedetomidine
Number of Participants With SpO2 < or Equal to 95%24
SecondaryParticipants Requiring Morphine Rescue in PACU
Time frame:
arrival in PACU to 2 hours postoperatively
Reported as:
Number · participants
Participants Requiring Morphine Rescue in PACU
participantsFentanylDexmedetomidine
Participants Requiring Morphine Rescue in PACU2511

Adverse events

Collected over 24 hours.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Fentanyl (F) Group—0/61 (0%)0/61 (0%)
Dexmedetomidine—1/61 (1.6%)0/61 (0%)
Most frequent serious events
Most frequent serious events
EventFentanyl (F) GroupDexmedetomidine
pulmonary edemaRespiratory, thoracic and mediastinal disorders0/611/61

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Fentanyl (F) GroupDexmedetomidineTotal
<=18 years6161122
Between 18 and 65 years000
>=65 years000
Age, Continuous
Age, Continuous(years)Fentanyl (F) GroupDexmedetomidineTotal
Mean3.8 ± 1.54.2 ± 2.14.0 ± 1.8
Sex: Female, Male
Sex: Female, Male(Participants)Fentanyl (F) GroupDexmedetomidineTotal
Female262652
Male353570
Region of Enrollment
Region of Enrollment(participants)Fentanyl (F) GroupDexmedetomidineTotal
United States6161122
08

Study locations

1 site
  • UMDNJ University Hospital
    Newark, New Jersey 07103, United States
09

References and documents

Publications

  • Isik B, Arslan M, Tunga AD, Kurtipek O. Dexmedetomidine decreases emergence agitation in pediatric patients after sevoflurane anesthesia without surgery. Paediatr Anaesth. 2006 Jul;16(7):748-53. doi: 10.1111/j.1460-9592.2006.01845.x. Erratum In: Paediatr Anaesth. 2006 Jul;16(7):811. PubMed 16879517 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Dec 5, 2016, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00468052
Lead sponsor
University of Medicine and Dentistry of New Jersey
Responsible party
Sponsor
First posted
May 1, 2007
Start date
Mar 2007
Primary completion
May 2008
Completion
May 2008
Results posted
Oct 11, 2016
Last update
Dec 5, 2016

Study contacts

Anuradha Patel, MD
principal investigator · University of Medicne & Dentistry of New Jersey

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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