Obstructive Sleep Apnea
Conditions
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
2 micrograms/kilogram as a bolus then 0.7 micrograms/kilogram infusion
1 microgram/kilogram as a bolus
Sponsors
Study design
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Emergence Agitation and Pain | On arrival to PACU and 2 hours postoperatively | 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 |
| Duration of Agitation | on arrival to PACU and for 2 hours postoperatively | Cole EA scale 1=calm , 5=unconsolable |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Extubation | at end of surgical procedure | defined as time from end of surgery to tracheal extubation |
| Hemodynamic Stability | intraoperatively | 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. |
| Participants Requiring Morphine Rescue in PACU | arrival 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 Awaken | at end of surgery | defined 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
| Arm | Count |
|---|---|
| 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 |
| Total | 122 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 7 | 8 |
Baseline characteristics
| Characteristic | Dexmedetomidine | Fentanyl (F) Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 61 Participants | 61 Participants | 122 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 4.2 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 participants | 61 participants | 122 participants |
| Sex: Female, Male Female | 26 Participants | 26 Participants | 52 Participants |
| Sex: Female, Male Male | 35 Participants | 35 Participants | 70 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 61 | 0 / 61 |
| serious Total, serious adverse events | 0 / 61 | 1 / 61 |
Outcome results
Duration of Agitation
Cole EA scale 1=calm , 5=unconsolable
Time frame: on arrival to PACU and for 2 hours postoperatively
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fentanyl (F) Group | Duration of Agitation | 11.85 minutes | Standard Deviation 12.02 |
| Dexmedetomidine | Duration of Agitation | 6.59 minutes | Standard Deviation 7.42 |
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
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Fentanyl (F) Group | Emergence Agitation and Pain | PAED | 14 units on a scale |
| Fentanyl (F) Group | Emergence Agitation and Pain | Cole EA | 4 units on a scale |
| Fentanyl (F) Group | Emergence Agitation and Pain | OPS | 5 units on a scale |
| Dexmedetomidine | Emergence Agitation and Pain | PAED | 10 units on a scale |
| Dexmedetomidine | Emergence Agitation and Pain | Cole EA | 3 units on a scale |
| Dexmedetomidine | Emergence Agitation and Pain | OPS | 3 units on a scale |
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
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fentanyl (F) Group | Hemodynamic Stability | heart rate below 60 bpm | 0 participants |
| Fentanyl (F) Group | Hemodynamic Stability | systolic blood pressure <30% below baseline | 0 participants |
| Dexmedetomidine | Hemodynamic Stability | heart rate below 60 bpm | 0 participants |
| Dexmedetomidine | Hemodynamic Stability | systolic blood pressure <30% below baseline | 0 participants |
Number of Participants With SpO2 < or Equal to 95%
Time frame: on arrival to PACU and 2 hours postoperatively
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fentanyl (F) Group | Number of Participants With SpO2 < or Equal to 95% | 2 participants |
| Dexmedetomidine | Number of Participants With SpO2 < or Equal to 95% | 4 participants |
Participants Requiring Morphine Rescue in PACU
Time frame: arrival in PACU to 2 hours postoperatively
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fentanyl (F) Group | Participants Requiring Morphine Rescue in PACU | 25 participants |
| Dexmedetomidine | Participants Requiring Morphine Rescue in PACU | 11 participants |
Time to Awaken
defined as spontaneous eye opening or on command
Time frame: at end of surgery
Population: per protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fentanyl (F) Group | Time to Awaken | 8.75 minutes | Standard Deviation 4.06 |
| Dexmedetomidine | Time to Awaken | 7.18 minutes | Standard Deviation 4.05 |
Time to Extubation
defined as time from end of surgery to tracheal extubation
Time frame: at end of surgical procedure
Population: per protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fentanyl (F) Group | Time to Extubation | 10.44 minutes | Standard Deviation 4.15 |
| Dexmedetomidine | Time to Extubation | 8.59 minutes | Standard Deviation 4.51 |