Pain
Conditions
Keywords
Painful medical procedures
Brief summary
The aim of the study is to investigate the absorption and clinical effect of nasal administration of an analgesic nasal spray containing sufentanil+ketamine for pain related to medical procedures in hospitalized children.
Detailed description
The management of procedural pain in children ranges from physical restraint to pharmacological interventions. Pediatric formulations that permit accurate dosing, are accepted by children and a have a rapid onset of analgesia are lacking. The objectives were to investigate a pediatric formulation of intranasal sufentanil 0.5 mcg/kg and ketamine 0.5 mg/kg for procedural pain and to characterize the pharmacokinetic (PK) profile. Fifty children (≥10 kg) scheduled for a painful procedure were included in this prospective nonrandomized open-label clinical trial. Thirteen of these children had central venous access for drug assay sampling; enabling a compartmental PK analysis using nonlinear mixed-effects models. Pain intensity before and during the procedure was measured using age-appropriate pain scales. Heart rate, oxygen saturation and sedation were recorded.
Interventions
DRUGIntranasal sufentanil/ketamine
Nasal spray sufentanil+ketamine, 0,5 microg/kg sufentanil+0,5 mg/kg ketamine, single dose
Sponsors
Rigshospitalet, Denmark
Danish University of Pharmaceutical Sciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 19 Years
Healthy volunteers
No
Inclusion criteria
* Children and adolescents treated at the University Hospital, Rigshospital * Painful medical procedure related to the patients treatment * Patient and/or the parents must be able to understand and speak danish * Negative pregnancy test for girls, when relevant * Signed informed consent * Only a light meals or no meals have been ingested 2 hours prior to inclusion
Exclusion criteria
* Allergy to sufentanil or ketamine * Abnormal nasal cavity * Have been treated with sufentanil and/or ketamine during the last 48 hours * Nasal obstruction (rhinitis)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Procedural Pain Intensity Score | Pain assessment during painful medical procedure | Children \<5 years old were administered the FLACC (Face Leg Activity Cry Consolability) Scale (Range: 0-10, where 0 is no pain and 10 is worst pain). Children \>= 5 years but \< 8 years old were administered the Visual analog scale modified with six faces by Wong-Baker (Wong-Baker Faces Pain Rating Scale) (Range: 0-10, where 0 is no pain and 10 is worst pain). Children \>= 8 years old were administered a Visual Analog Scale (Range: 0-10, where 0 is no pain and 10 is worst pain). |
| Maximum Plasma Concentration (Cmax) of Sufentanil and Ketamine | Time= 5-60 min after administration of the investigational medical product | — |
| Bioavailability of Sufentanil and Ketamine | Time= 5-60 min after administration of the investigational medical product | — |
| Time to Maximum Plasma Concentrations (Tmax) Sufentanil and Ketamine | Time=5-60 min after administration of investigational medicinal product | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sedation Score (UMSS) | Time= 0-70 min. after drug administration | University of Michigan Sedation Score (UMSS) (0-4, 0 awake and alert, 4 unarousable) |
| Acceptance of Intranasal Administration | Immediately after the procedure | Asking the children (parents for preverbal children) if they would like to receive this treatment again in a similar situation rather than analgesic suppositories, tablets, oral solutions, or injections? |
Countries
Denmark
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Intranasal Sufentanil+Ketamine Sufentanil, ketamine: Nasal spray sufentanil+ketamine, single dose | 50 |
| Total | 50 |
Baseline characteristics
| Characteristic | Intranasal Sufentanil+Ketamine |
|---|---|
| Age, Continuous | 8.8 years STANDARD_DEVIATION 4.9 |
| Height | 138.4 cm STANDARD_DEVIATION 32 |
| Preprocedural pain intensity | 0.0 units on a scale |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 36 Participants |
| Weight | 34.9 kg STANDARD_DEVIATION 20.1 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 2 / 50 |
| serious Total, serious adverse events | 0 / 50 |
Outcome results
Primary
Bioavailability of Sufentanil and Ketamine
Time frame: Time= 5-60 min after administration of the investigational medical product
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Intranasal Sufentanil/Ketamine | Bioavailability of Sufentanil and Ketamine | Bioavailability sufentanil | 24.6 percentage bioavailable | Standard Error 18.5 |
| Intranasal Sufentanil/Ketamine | Bioavailability of Sufentanil and Ketamine | Bioavailability ketamine | 35.8 percentage bioavailable | Standard Error 15.4 |
Primary
Maximum Plasma Concentration (Cmax) of Sufentanil and Ketamine
Time frame: Time= 5-60 min after administration of the investigational medical product
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Intranasal Sufentanil/Ketamine | Maximum Plasma Concentration (Cmax) of Sufentanil and Ketamine | Cmax sufentanil | 0.042 mcg/L | Standard Deviation 0.005 |
| Intranasal Sufentanil/Ketamine | Maximum Plasma Concentration (Cmax) of Sufentanil and Ketamine | Cmax ketamine | 102 mcg/L | Standard Deviation 11 |
Primary
Procedural Pain Intensity Score
Children \<5 years old were administered the FLACC (Face Leg Activity Cry Consolability) Scale (Range: 0-10, where 0 is no pain and 10 is worst pain). Children \>= 5 years but \< 8 years old were administered the Visual analog scale modified with six faces by Wong-Baker (Wong-Baker Faces Pain Rating Scale) (Range: 0-10, where 0 is no pain and 10 is worst pain). Children \>= 8 years old were administered a Visual Analog Scale (Range: 0-10, where 0 is no pain and 10 is worst pain).
Time frame: Pain assessment during painful medical procedure
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Intranasal Sufentanil/Ketamine | Procedural Pain Intensity Score | 3.1 units on a scale |
Primary
Time to Maximum Plasma Concentrations (Tmax) Sufentanil and Ketamine
Time frame: Time=5-60 min after administration of investigational medicinal product
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Intranasal Sufentanil/Ketamine | Time to Maximum Plasma Concentrations (Tmax) Sufentanil and Ketamine | Tmax sufentanil | 13.8 minutes | Standard Deviation 1.7 |
| Intranasal Sufentanil/Ketamine | Time to Maximum Plasma Concentrations (Tmax) Sufentanil and Ketamine | Tmax ketamine | 8.5 minutes | Standard Deviation 1.5 |
Secondary
Acceptance of Intranasal Administration
Asking the children (parents for preverbal children) if they would like to receive this treatment again in a similar situation rather than analgesic suppositories, tablets, oral solutions, or injections?
Time frame: Immediately after the procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intranasal Sufentanil/Ketamine | Acceptance of Intranasal Administration | 47 percentage of participants |
Secondary
Sedation Score (UMSS)
University of Michigan Sedation Score (UMSS) (0-4, 0 awake and alert, 4 unarousable)
Time frame: Time= 0-70 min. after drug administration
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Intranasal Sufentanil/Ketamine | Sedation Score (UMSS) | 0 units on a scale |