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

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.

Study Overview

• Status: Completed
• Conditions: Obstructive Sleep Apnea
• Intervention / Treatment: Drug: fentanyl; Drug: dexmedetomidine

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.

• Study Type: Interventional
• Enrollment (Actual): 122
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Newark, New Jersey, United States, 07103
      • UMDNJ University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 10 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: fentanyl; fentanyl bolus 1ug.kg-1	Drug: fentanyl; 1 microgram/kilogram as a bolus; Other Names: Sublimaze
Experimental: dexmedetomidine; dexmedetomidine 2ug.kg-1 over 10 min followed by 0.7ug.kg-1.h-1	Drug: dexmedetomidine; 2 micrograms/kilogram as a bolus then 0.7 micrograms/kilogram infusion; Other Names: Precedex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	On arrival to PACU and 2 hours postoperatively
Duration of Agitation	Cole EA scale 1=calm , 5=unconsolable	on arrival to PACU and for 2 hours postoperatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	intraoperatively
Time to Awaken	defined as spontaneous eye opening or on command	at end of surgery
Time to Extubation	defined as time from end of surgery to tracheal extubation	at end of surgical procedure
Number of Participants With SpO2 < or Equal to 95%		on arrival to PACU and 2 hours postoperatively
Participants Requiring Morphine Rescue in PACU		arrival in PACU to 2 hours postoperatively

Collaborators and Investigators

• Sponsor: University of Medicine and Dentistry of New Jersey
• Investigators: Principal Investigator: Anuradha Patel, MD, University of Medicne & Dentistry of New Jersey

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start: March 1, 2007
• Primary Completion (Actual): May 1, 2008
• Study Completion (Actual): May 1, 2008

Study Registration Dates

• First Submitted: April 27, 2007
• First Submitted That Met QC Criteria: April 30, 2007
• First Posted (Estimate): May 1, 2007

Study Record Updates

• Last Update Posted (Estimate): December 5, 2016
• Last Update Submitted That Met QC Criteria: October 11, 2016
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Keywords: obstructive sleep apnea; tonsillectomy; adenoidectomy
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Respiratory Tract Diseases; Apnea; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Postoperative Complications; Neurologic Manifestations; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Delirium; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Emergence Delirium; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Analgesics, Opioid; Narcotics; Hypnotics and Sedatives; Adjuvants, Anesthesia; Fentanyl; Dexmedetomidine
• Other Study ID Numbers: 0120060313