Psychomotor Agitation
Conditions
Keywords
Anaesthesia, Children, Clonidine, Sevoflurane, Postoperative agitation, Prevention, Pharmacokinetics, Safety
Brief summary
Clonidine is widely used off-label in children for several indications. Clonidine is used for treatment and/or prevention of postoperative agitation in children anaesthetised with Sevoflurane. The investigators don´t have solid evidence for the effect and the investigators don´t have data for characterization of the pharmacokinetic profile among age-groups for children 1-6 years. In this study the investigators want to investigate if IV Clonidine administered at the end of surgery can prevent/reduce postoperative agitation. Secondary outcomes include measurements of postoperative pain relief and adverse effects, including a 30-day follow-up.
Detailed description
BACKGROUND: Clonidine is widely used off-label in children for several indications such as treatment and/or prevention of postoperative agitation when anaesthetised with Sevoflurane. However, the current level of evidence in support of Clonidine treatment for postoperative agitation in children remains limited. In addition, the pharmacokinetic profile of intravenous Clonidine in children is not well characterized for age-groups. METHODS/DESIGN: In this prospective multicentre double-blinded randomized clinical trial, the investigators aim to investigate the impact of intravenous (IV) Clonidine administered at the end of surgery, on the incidence and degree of postoperative agitation. Children will be assigned to either the intervention or the placebo group. The allocation will be carried out centrally and stratified based on age and trial-site, with152 patients allocated to each group. In the intervention group, 3 micrograms per kg of IV clonidine is administered approximately 20 minutes before the expected completion of the surgery (as assessed by the surgeon). In the control group; Saline (placebo) is injected in equal quantity during surgery at the same time. The drugs are concealed in identical blinded ampoules. The primary outcome is postoperative agitation measured on the Watcha scale. Secondary outcomes include measurements of postoperative pain relief and adverse effects, including 30-day follow-up. Twenty of the patients age 1-2 years and twenty age \>2 years, with a peripheral venous access in place, will be allocated to drug assay sampling; enabling a compartmental PK analysis based on age group, using non-linear mixed effects models.
Interventions
DRUGClonidine
Injection - during surgery
DRUGPlacebo
Injection - during surgery
Sponsors
Rigshospitalet, Denmark
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
1 Years to 5 Years
Healthy volunteers
No
Inclusion criteria
* scheduled for surgery with Sevoflurane as the choice of anesthesia.
Exclusion criteria
* ASA classification \>2 * Premedication with Clonidine * Ex-premature (born before week 37+0 AND \<60 weeks old) * Intubated before anaesthesia and/or no plans for extubation after anaesthesia. * Critical illness with haemodynamic instability. * Active bleeding. * Cancer. * Cardiac diseases including arrhythmias. * Malignant hyperthermia. * Mental retardation. * Neurological illness with agitation-like symptoms. * Weight \>50 kg. * Allergy to Clonidine. * Patients treated with methylphenidate / Concerta.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Postoperative Agitation | 1 day | Measured by Watchae Scale (score 1-4), scores 1-2 = no agitation and scores 3-4 = agitated |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fentanyl and Morphine Requirements | Recorded during the stay in the postoperative recovery room | Amount used |
| Pain Assessment | recovery room - hours | Pain score used: FLACC score = Face, Legs, Activity, Cry, Consolability Score ranges from 0 to 10 (severity increases with increasing score) Pain is FLACC score more than 3 |
| First Administration of Fentanyl or Morphine | recovery room | Time to administration |
| Adverse Events | from intervention to discharge from the recovery room | — |
Countries
Denmark
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Intervention Clonidine : injection og 3 micg/kg IV during the operation.
Clonidine: Injection - during surgery | 191 |
| Placebo Placebo : injection og equal amount of NaCl IV during the operation.
Placebo: Injection - during surgery | 188 |
| Total | 379 |
Baseline characteristics
| Characteristic | Intervention | Placebo | Total |
|---|---|---|---|
| Age, Customized < 2 years | 46 participants | 43 participants | 89 participants |
| Age, Customized >/= 2 years | 145 participants | 145 participants | 290 participants |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment Denmark | 191 participants | 188 participants | 379 participants |
| Sex: Female, Male Female | 37 Participants | 38 Participants | 75 Participants |
| Sex: Female, Male Male | 154 Participants | 150 Participants | 304 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 191 | 0 / 188 |
| other Total, other adverse events | 0 / 191 | 5 / 188 |
| serious Total, serious adverse events | 2 / 191 | 2 / 188 |
Outcome results
Primary
Postoperative Agitation
Measured by Watchae Scale (score 1-4), scores 1-2 = no agitation and scores 3-4 = agitated
Time frame: 1 day
Population: 9 were excluded in the primary outcome due to missing data points
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intervention | Postoperative Agitation | 46 participants with agitation |
| Placebo | Postoperative Agitation | 86 participants with agitation |
Secondary
Adverse Events
Time frame: from intervention to discharge from the recovery room
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Intervention | Adverse Events | adverse events | 0 participants |
| Intervention | Adverse Events | serious adverse events | 2 participants |
| Intervention | Adverse Events | Treated for low blood pressure | 0 participants |
| Placebo | Adverse Events | adverse events | 5 participants |
| Placebo | Adverse Events | serious adverse events | 2 participants |
| Placebo | Adverse Events | Treated for low blood pressure | 0 participants |
Secondary
Fentanyl and Morphine Requirements
Amount used
Time frame: Recorded during the stay in the postoperative recovery room
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention | Fentanyl and Morphine Requirements | 0.46 mg morphine equivalents | Standard Deviation 0.94 |
| Placebo | Fentanyl and Morphine Requirements | 0.7 mg morphine equivalents | Standard Deviation 1.11 |
Secondary
First Administration of Fentanyl or Morphine
Time to administration
Time frame: recovery room
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Intervention | First Administration of Fentanyl or Morphine | 105 MEDIAN time (min) to administration | Standard Deviation 57 |
| Placebo | First Administration of Fentanyl or Morphine | 60 MEDIAN time (min) to administration | Standard Deviation 46 |
Secondary
Pain Assessment
Pain score used: FLACC score = Face, Legs, Activity, Cry, Consolability Score ranges from 0 to 10 (severity increases with increasing score) Pain is FLACC score more than 3
Time frame: recovery room - hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention | Pain Assessment | 1.57 Pain Score | Standard Deviation 2.62 |
| Placebo | Pain Assessment | 2.45 Pain Score | Standard Deviation 3.1 |