Anesthesia, Local
Conditions
Keywords
Ropivacaine, Erector spinae plane block, Pediatric
Brief summary
The primary aim of this study is to evaluate the pharmacokinetics of serum ropivacaine concentrations following erector spinae plane peripheral nerve blocks in the pediatric population. Secondary outcomes will assess the efficacy of the block with perioperative morphine equivalent consumption and pain scores.
Detailed description
This pilot study will enroll patients at Texas Children's Hospital, aged 6 months to \<18 years scheduled to undergo a clinically indicated thoracic surgery with the adjunct of an erector spinae plane block for perioperative pain. A single shot erector spinae plane block is commonly offered for unilateral video-assisted thoracoscopic surgery (VATS) and unilateral chest tube insertions. Following parental consent and child assent to the block, participants will be assigned sequentially to either ropivacaine 0.2% at 0.3ml/kg or ropivacaine 0.5% at 0.3ml/kg. This pilot study poses no additional risk to the patient and the thoracic surgical procedures outlined are those for which an erector spinae plane block would be offered. Furthermore, the block dosing of 0.3ml/kg volumes with ropivacaine 0.2% or 0.5% are not outside of the standard of care or accepted dosages for peripheral nerve blocks. Venous sample serum ropivacaine levels will be collected prior to ESP block and at 30, 60, 90-minutes and 2, 4, 6 -hours from intravenous access in situ. A baseline alpha-1 acid glycoprotein (AGP) test will be collected and processed by TCH Pathology. Amide local anesthetics are predominantly protein bound to AGP. It is the unbound form that is active. While this study seeks to understand the pharmacokinetics of ropivacaine following a single shot erector spinae plane block, correlate of the AGP will simultaneously ascertain the free vs bound portion. Samples will be analyzed for the total and free serum ropivacaine concentrations. Pain scores will be collected from nursing records starting from arrival in the Post-Anesthesia Care Unit every 4 hours (up to 12 hours after arrival in PACU). Pain will be measured using The Face, Legs, Activity, Cry, Consolability scale (FLACC), the Wong-Baker FACES Pain Rating Scale (FACES), and the Visual Analogue Scale (VAS).
Interventions
DRUGRopivacaine
Given the reproducible efficacy of the erector spinae plane block for thoracic procedures, this pilot study will recruit patients scheduled to undergo thoracic surgery with the adjunct of an erector spinae plane block for perioperative pain. Participants will be assigned sequentially to either ropivacaine 0.2% at 0.3ml/kg or ropivacaine 0.5% at 0.3ml/kg.
Sponsors
Baylor College of Medicine
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Intervention model description
Participants will be assigned to either ropivacaine 0.2% at 0.3ml/kg or ropivacaine 0.5% at 0.3ml/kg on an odd/even basis
Eligibility
Sex/Gender
ALL
Age
6 Months to 18 Years
Healthy volunteers
No
Inclusion criteria
* Age: 6 months - \< 18 years old; * Chest tubes or minimally invasive video assisted thoracic surgery; * Surgery scheduled between 7AM and 5PM * Weight greater than 4kg
Exclusion criteria
* Renal dysfunction; * Liver dysfunction; * Hypoalbuminemia; * Allergy to local anesthetic; * Spinal hardware or instrumentation; * Scoliosis; * Obesity defined as a BMI \>95% percentile
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ropivacaine Concentrations | Prior to administration and at 30, 60, 90-minutes and 2, 4, 6-hours following intravenous access in situ | Pharmacokinetics(PK) of free and total serum ropivacaine concentrations following erector spinae plane peripheral nerve block administration. Blood samples were drawn at the indicated time points for each subject. Laboratory assays will be completed and resulted for all subject samples collected. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Post-anesthesia Care Unit Pain Scores Using FLACC Scale | Every 4 hours (up to 12 hours after arrival in PACU) | The Face, Legs, Activity, Cry, Consolability Scale (FLACC) is a measurement used to assess pain for children between the ages of 2 months and 7 years or individuals that are unable to communicate their pain. The scale is scored in a range of 0-10 with 0 representing no pain. The scale has five criteria, which are each assigned a score of 0, 1 or 2. Scores will be tracked from nursing inputs. There scale was utilized for one subject. The measure data was collected \<2 hours post-op. |
| Post-anesthesia Care Unit Pain Scores Using FACES Pain Rating Scale | Every 4 hours (up to 12 hours after arrival in PACU) | The FACES Pain Rating Scale is a tool originally created for children to help them communicate their pain. Now the scale is used around the world with people ages 3 and older. The scale uses 6 faces scored 0-10 with 0 representing no pain. Each facial criteria increases by a score of 2. Scores will be tracked from nursing inputs. There was no data collected for this measure as this scale was not used. Subjects were assessed with a different validated Pain Scale, not data was collected using this scale. |
| Post-anesthesia Care Unit Pain Scores Using VAS | Every 4 hours (up to 12 hours after arrival in PACU) | The visual analog scale (VAS) is a validated, subjective measure for acute and chronic pain. Scores are recorded by making a handwritten mark on a 10-cm line that represents a continuum between no pain and worst pain. A score of 0 represents no pain and 10 represents the worst the pain could be. Scores will be tracked from nursing inputs. |
| Morphine Equivalents | 12 hours | Consumption of morphine per subject was collected post-operatively. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Serum Alpha Acid Glycoprotein(AAG) Level | Pre-op | Serum alpha acid glycoprotein levels were analyzed with serum ropivacaine concentrations. No additional samples were collected for AAG levels but laboratory analysis was completed simultaneously with ropivacaine concentrations. |
Countries
United States
Participant flow
Recruitment details
Subjects enrolled from the hospital pre-op area. The enrollment period from Dec. 2020 to January 2021. The initial subject was enrolled on Dec. 18, 2020 and the last enrolled on January 27, 2021. All subjects enrolled met the inclusion criteria and were dosed with 0.5% ropivacaine.
Pre-assignment details
No subjects were enrolled into the Ropivicaine 0.2% at 0.3mL/kg arm.
Participants by arm
| Arm | Count |
|---|---|
| Ropivacaine 0.2% at 0.3ml/kg Ropivacaine 0.2% at 0.3ml/kg
Ropivacaine: Given the reproducible efficacy of the erector spinae plane block for thoracic procedures, this pilot study will recruit patients scheduled to undergo thoracic surgery with the adjunct of an erector spinae plane block for perioperative pain. Participants will be assigned sequentially to either ropivacaine 0.2% at 0.3ml/kg or ropivacaine 0.5% at 0.3ml/kg. | 0 |
| Ropivacaine 0.5% at 0.3ml/kg Ropivacaine 0.5% at 0.3ml/kg
Ropivacaine: Given the reproducible efficacy of the erector spinae plane block for thoracic procedures, this pilot study will recruit patients scheduled to undergo thoracic surgery with the adjunct of an erector spinae plane block for perioperative pain. Participants will be assigned sequentially to either ropivacaine 0.2% at 0.3ml/kg or ropivacaine 0.5% at 0.3ml/kg. | 4 |
| Total | 4 |
Baseline characteristics
| Characteristic | Ropivacaine 0.2% at 0.3ml/kg | Ropivacaine 0.5% at 0.3ml/kg | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 4 Participants | 4 Participants |
| Age, Categorical >=65 years | — | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | — | 0 Participants | 0 Participants |
| Dose ropivacaine 0.5% at 0.3mL/kg Dose (Subj. 1) | — | 84.3 ng/mL | 84.3 ng/mL |
| Dose ropivacaine 0.5% at 0.3mL/kg Dose (Subj. 2) | — | 33.15 ng/mL | 33.15 ng/mL |
| Dose ropivacaine 0.5% at 0.3mL/kg Dose (Subj. 3) | — | 11.50 ng/mL | 11.50 ng/mL |
| Dose ropivacaine 0.5% at 0.3mL/kg Dose (Subj. 4) | — | 9.37 ng/mL | 9.37 ng/mL |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment United States | — | 4 participants | 4 participants |
| Sex: Female, Male Female | 0 Participants | 3 Participants | 3 Participants |
| Sex: Female, Male Male | 0 Participants | 1 Participants | 1 Participants |
| Weight(kg) weight (subject 1) | — | 56.2 kg | 56.2 kg |
| Weight(kg) weight (subject 2) | — | 22.1 kg | 22.1 kg |
| Weight(kg) weight (subject 3) | — | 9.6 kg | 9.6 kg |
| Weight(kg) weight (subject 4) | — | 53.8 kg | 53.8 kg |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 4 | 0 / 4 |
| other Total, other adverse events | 0 / 0 | 0 / 4 | 0 / 4 |
| serious Total, serious adverse events | 0 / 0 | 0 / 4 | 0 / 4 |
Outcome results
Primary
Ropivacaine Concentrations
Pharmacokinetics(PK) of free and total serum ropivacaine concentrations following erector spinae plane peripheral nerve block administration. Blood samples were drawn at the indicated time points for each subject. Laboratory assays will be completed and resulted for all subject samples collected.
Time frame: Prior to administration and at 30, 60, 90-minutes and 2, 4, 6-hours following intravenous access in situ
Population: All participants were given a 0.5% concentration of ropivacaine at 0.3mL/kg. PK blood samples drawn from baseline( prior to administration)up to 6 hours post dose.~Serum concentrations was were compared across time points using the non linear mixed-effects modeling(NONREM) approach. Sode/serum concentration simulations was also utilized in analysis. Data will be reported as either mean, standard deviation or median and interquartile range as appropriate.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Total Ropivacaine Concentration (ng/mL) | Ropivacaine Concentrations | Time (30min post administration) | 1232.25 ng/mL | Standard Deviation 282.2 |
| Total Ropivacaine Concentration (ng/mL) | Ropivacaine Concentrations | Time (90 min post administration) | 949.5 ng/mL | Standard Deviation 100.1 |
| Total Ropivacaine Concentration (ng/mL) | Ropivacaine Concentrations | Time (60 min post administration) | 776.25 ng/mL | Standard Deviation 318.57 |
| Total Ropivacaine Concentration (ng/mL) | Ropivacaine Concentrations | Time (120 min post administration) | 779.5 ng/mL | Standard Deviation 386.24 |
| Total Ropivacaine Concentration (ng/mL) | Ropivacaine Concentrations | Time (Baseline/Trough) | 0 ng/mL | Standard Deviation 0 |
| Total Ropivacaine Concentration (ng/mL) | Ropivacaine Concentrations | Time (360 min post administration) | 780.5 ng/mL | Standard Deviation 336.5 |
| Total Ropivacaine Concentration (ng/mL) | Ropivacaine Concentrations | Time (240 min post administration) | 684 ng/mL | Standard Deviation 425.62 |
| Free Ropivacaine Concentration (ng/mL) | Ropivacaine Concentrations | Time (360 min post administration) | 509 ng/mL | Standard Deviation 146 |
| Free Ropivacaine Concentration (ng/mL) | Ropivacaine Concentrations | Time (90 min post administration) | 631 ng/mL | Standard Deviation 174.73 |
| Free Ropivacaine Concentration (ng/mL) | Ropivacaine Concentrations | Time (240 min post administration) | 417 ng/mL | Standard Deviation 229.83 |
| Free Ropivacaine Concentration (ng/mL) | Ropivacaine Concentrations | Time (Baseline/Trough) | 0 ng/mL | Standard Deviation 0 |
| Free Ropivacaine Concentration (ng/mL) | Ropivacaine Concentrations | Time (30min post administration) | 850.25 ng/mL | Standard Deviation 187.19 |
| Free Ropivacaine Concentration (ng/mL) | Ropivacaine Concentrations | Time (120 min post administration) | 468.25 ng/mL | Standard Deviation 202.1 |
| Free Ropivacaine Concentration (ng/mL) | Ropivacaine Concentrations | Time (60 min post administration) | 518 ng/mL | Standard Deviation 151.33 |
Secondary
Morphine Equivalents
Consumption of morphine per subject was collected post-operatively.
Time frame: 12 hours
Population: Morphine milligram equivalents(MME) obtained on each participant that was administered ropivacaine dose. MME obtained post- operatively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ropivacaine 0.2% at 0.3ml/kg | Morphine Equivalents | Subject 1 - MME | 5 mg |
| Ropivacaine 0.2% at 0.3ml/kg | Morphine Equivalents | Subject 2- MME | 1.68 mg |
| Ropivacaine 0.2% at 0.3ml/kg | Morphine Equivalents | Subject 3 - MME | 0 mg |
| Ropivacaine 0.2% at 0.3ml/kg | Morphine Equivalents | Subject 4 - MME | 6 mg |
Secondary
Post-anesthesia Care Unit Pain Scores Using FACES Pain Rating Scale
The FACES Pain Rating Scale is a tool originally created for children to help them communicate their pain. Now the scale is used around the world with people ages 3 and older. The scale uses 6 faces scored 0-10 with 0 representing no pain. Each facial criteria increases by a score of 2. Scores will be tracked from nursing inputs. There was no data collected for this measure as this scale was not used. Subjects were assessed with a different validated Pain Scale, not data was collected using this scale.
Time frame: Every 4 hours (up to 12 hours after arrival in PACU)
Population: Subjects pain scores were collected using a different validated pain scale.
Secondary
Post-anesthesia Care Unit Pain Scores Using FLACC Scale
The Face, Legs, Activity, Cry, Consolability Scale (FLACC) is a measurement used to assess pain for children between the ages of 2 months and 7 years or individuals that are unable to communicate their pain. The scale is scored in a range of 0-10 with 0 representing no pain. The scale has five criteria, which are each assigned a score of 0, 1 or 2. Scores will be tracked from nursing inputs. There scale was utilized for one subject. The measure data was collected \<2 hours post-op.
Time frame: Every 4 hours (up to 12 hours after arrival in PACU)
Population: Scale utilized as developmentally age appropriate.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ropivacaine 0.2% at 0.3ml/kg | Post-anesthesia Care Unit Pain Scores Using FLACC Scale | 0 score on a scale |
Secondary
Post-anesthesia Care Unit Pain Scores Using VAS
The visual analog scale (VAS) is a validated, subjective measure for acute and chronic pain. Scores are recorded by making a handwritten mark on a 10-cm line that represents a continuum between no pain and worst pain. A score of 0 represents no pain and 10 represents the worst the pain could be. Scores will be tracked from nursing inputs.
Time frame: Every 4 hours (up to 12 hours after arrival in PACU)
Population: The assessment was used when developmentally age appropriate. This scale was not used in the assessment of one subject, 3 subjects were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ropivacaine 0.2% at 0.3ml/kg | Post-anesthesia Care Unit Pain Scores Using VAS | Subj. 1- Numeric Pain score < 2 hours post op | 5 score on a scale |
| Ropivacaine 0.2% at 0.3ml/kg | Post-anesthesia Care Unit Pain Scores Using VAS | Subj.2- Numeric Pain score < 2 hours post-op | 1.68 score on a scale |
| Ropivacaine 0.2% at 0.3ml/kg | Post-anesthesia Care Unit Pain Scores Using VAS | Subj. 4- Numeric Pain score < 2 hours post-op | 6 score on a scale |
Other Pre-specified
Serum Alpha Acid Glycoprotein(AAG) Level
Serum alpha acid glycoprotein levels were analyzed with serum ropivacaine concentrations. No additional samples were collected for AAG levels but laboratory analysis was completed simultaneously with ropivacaine concentrations.
Time frame: Pre-op
Population: A sample was not collected for Subject 1
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ropivacaine 0.2% at 0.3ml/kg | Serum Alpha Acid Glycoprotein(AAG) Level | Subject 2 | 65 mg/dL |
| Ropivacaine 0.2% at 0.3ml/kg | Serum Alpha Acid Glycoprotein(AAG) Level | Subject 3 | 47 mg/dL |
| Ropivacaine 0.2% at 0.3ml/kg | Serum Alpha Acid Glycoprotein(AAG) Level | Subject 4 | 71 mg/dL |