Pain Relief for Children Undergoing Tonsillectomy & Adenoidectomy

Obstructive Sleep Apnea Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00468052
• Other study ID #: 0120060313
• Status: Completed
• Phase: Phase 3
• First received: April 27, 2007
• Last updated: November 30, 2010
• Start date: March 2007
• Est. completion date: May 2008

Study information

• Verified date: November 2010
• Source: Rutgers, The State University of New Jersey
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 122
• Est. completion date: May 2008
• Est. primary completion date: May 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years to 10 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Obstructive Sleep Apnea
• Sleep Apnea, Obstructive

Intervention

Drug:
• dexmedetomidine
2 micrograms/kilogram as a bolus then 0.7 micrograms/kilogram infusion
• fentanyl
1 microgram/kilogram as a bolus

Locations

Country	Name	City	State
United States	UMDNJ University Hospital	Newark	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
University of Medicine and Dentistry of New Jersey

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. Erratum in: Paediatr Anaesth. 2006 Jul;16(7):811. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	vital signs (Heart rate, blood pressure, oxygen sat,respiratory rate, end title carbon dioxide, BIS)at five minute intervals perioperatively		5 minute intervals postoperatively	Yes
Primary	time to awakening		following end of anesthetic medication	Yes
Primary	time to extubation		after awakening	Yes
Primary	Pain and emergent agitation tool		2 hours postoperatively	No
Secondary	Objective Pain Scale and use of rescue medication		2 hours postoperatively	Yes
Secondary	Pediatric Anesthesia Emergence Delirium		2 hours postoperatively	Yes
Secondary	Post operative Emesis		2 hours postoperatively	Yes