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

Use of Dexmedetomidine Infusion for Analgesia and Emergence Agitation for Children Undergoing Tonsillectomy and Adenotonsillectomy

Status
Completed
Phases
Phase 3
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00468052
Enrollment
122
Registered
2007-05-01
Start date
2007-03-31
Completion date
2008-05-31
Last updated
2016-12-05

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

Conditions

Obstructive Sleep Apnea

Keywords

obstructive sleep apnea, tonsillectomy, adenoidectomy

Brief 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.

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.

Interventions

DRUGdexmedetomidine

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

DRUGfentanyl

1 microgram/kilogram as a bolus

Sponsors

University of Medicine and Dentistry of New Jersey
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Subject)

Eligibility

Sex/Gender
ALL
Age
2 Years to 10 Years
Healthy volunteers
No

Inclusion criteria

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

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

Design outcomes

Primary

MeasureTime frameDescription
Emergence Agitation and PainOn arrival to PACU and 2 hours postoperativelyemergence 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
Duration of Agitationon arrival to PACU and for 2 hours postoperativelyCole EA scale 1=calm , 5=unconsolable

Secondary

MeasureTime frameDescription
Time to Extubationat end of surgical proceduredefined as time from end of surgery to tracheal extubation
Hemodynamic StabilityintraoperativelyParticipants 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.
Participants Requiring Morphine Rescue in PACUarrival in PACU to 2 hours postoperatively
Number of Participants With SpO2 < or Equal to 95%on arrival to PACU and 2 hours postoperatively
Time to Awakenat end of surgerydefined as spontaneous eye opening or on command

Countries

United States

Participant flow

Recruitment details

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.

Pre-assignment details

None as long as the subject fit the inclusion criteria

Participants by arm

ArmCount
Fentanyl (F) Group
61 subjects in group F received IV (1mcg/kg)as a bolus as soon as IV access was established. 0
61
Dexmedetomidine
61 subjects Group D received IV dexmedetomidine 2mcg/kg over 10 minutes followed by an infusion of 0.7mcg.kg/hr
61
Total122

Withdrawals & dropouts

PeriodReasonFG000FG001
Overall StudyProtocol Violation78

Baseline characteristics

CharacteristicDexmedetomidineFentanyl (F) GroupTotal
Age, Categorical
<=18 years
61 Participants61 Participants122 Participants
Age, Categorical
>=65 years
0 Participants0 Participants0 Participants
Age, Categorical
Between 18 and 65 years
0 Participants0 Participants0 Participants
Age, Continuous4.2 years
STANDARD_DEVIATION 2.1
3.8 years
STANDARD_DEVIATION 1.5
4.0 years
STANDARD_DEVIATION 1.8
Region of Enrollment
United States
61 participants61 participants122 participants
Sex: Female, Male
Female
26 Participants26 Participants52 Participants
Sex: Female, Male
Male
35 Participants35 Participants70 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
— / —— / —
other
Total, other adverse events
0 / 610 / 61
serious
Total, serious adverse events
0 / 611 / 61

Outcome results

Primary

Duration of Agitation

Cole EA scale 1=calm , 5=unconsolable

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

ArmMeasureValue (MEAN)Dispersion
Fentanyl (F) GroupDuration of Agitation11.85 minutesStandard Deviation 12.02
DexmedetomidineDuration of Agitation6.59 minutesStandard Deviation 7.42
p-value: 0.004Wilcoxon (Mann-Whitney)
Primary

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

Population: per protocol, OPS, PAED and Cole scale are expressed as median values of the maximum score

ArmMeasureGroupValue (MEDIAN)
Fentanyl (F) GroupEmergence Agitation and PainPAED14 units on a scale
Fentanyl (F) GroupEmergence Agitation and PainCole EA4 units on a scale
Fentanyl (F) GroupEmergence Agitation and PainOPS5 units on a scale
DexmedetomidineEmergence Agitation and PainPAED10 units on a scale
DexmedetomidineEmergence Agitation and PainCole EA3 units on a scale
DexmedetomidineEmergence Agitation and PainOPS3 units on a scale
Comparison: Sixty subjects were required per group to determine that with Dex would decrease the incidence of severe EA after surgery by 50% with 80% power (0.05)in comparison with the control group.60 subjects were required by group to show the that intraoperative rescue fentanyl and rescue morphine in the PACU would be 50% lower in subjects receiving dex.p-value: 0.001Wilcoxon (Mann-Whitney)
Comparison: Null hypothesis dexmedetomidine would be a safe and effective substitute to opiates in reducing pain and the incidence of severe EAp-value: 0.001Wilcoxon (Mann-Whitney)
Secondary

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

ArmMeasureGroupValue (NUMBER)
Fentanyl (F) GroupHemodynamic Stabilityheart rate below 60 bpm0 participants
Fentanyl (F) GroupHemodynamic Stabilitysystolic blood pressure <30% below baseline0 participants
DexmedetomidineHemodynamic Stabilityheart rate below 60 bpm0 participants
DexmedetomidineHemodynamic Stabilitysystolic blood pressure <30% below baseline0 participants
Secondary

Number of Participants With SpO2 < or Equal to 95%

Time frame: on arrival to PACU and 2 hours postoperatively

ArmMeasureValue (NUMBER)
Fentanyl (F) GroupNumber of Participants With SpO2 < or Equal to 95%2 participants
DexmedetomidineNumber of Participants With SpO2 < or Equal to 95%4 participants
Secondary

Participants Requiring Morphine Rescue in PACU

Time frame: arrival in PACU to 2 hours postoperatively

ArmMeasureValue (NUMBER)
Fentanyl (F) GroupParticipants Requiring Morphine Rescue in PACU25 participants
DexmedetomidineParticipants Requiring Morphine Rescue in PACU11 participants
Secondary

Time to Awaken

defined as spontaneous eye opening or on command

Time frame: at end of surgery

Population: per protocol

ArmMeasureValue (MEAN)Dispersion
Fentanyl (F) GroupTime to Awaken8.75 minutesStandard Deviation 4.06
DexmedetomidineTime to Awaken7.18 minutesStandard Deviation 4.05
p-value: 0.03Fisher Exact
Secondary

Time to Extubation

defined as time from end of surgery to tracheal extubation

Time frame: at end of surgical procedure

Population: per protocol

ArmMeasureValue (MEAN)Dispersion
Fentanyl (F) GroupTime to Extubation10.44 minutesStandard Deviation 4.15
DexmedetomidineTime to Extubation8.59 minutesStandard Deviation 4.51
p-value: 0.02Fisher Exact

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026