Electroencephalography, Infant, Newborn, Infant, Premature, Pain Management, Pain Measurement, Pain Perception
Conditions
Brief summary
The assessment and treatment of pain in neonates remains a challenge. In an effort to improve the quality of care while limiting opioid-related adverse effects, this study aims to determine the efficacy of a non-pharmacological intervention on the mitigation of nociception-specific responses to a skin breaking procedure in term and preterm neonates. Such responses will be measured using behavioral measures as well as with electroencephalography-based methods.
Detailed description
Eligible neonates who are 36-56 weeks post-menstrual age and who are scheduled to undergo a clinically required heel lance will be studied after obtaining appropriate verbal and written consent from the respective parents. Subjects will be monitored during a baseline resting state, during vibratory stimuli alone, and during a heel lance that is randomized to be preceded or not preceded by the vibratory stimulus. The sessions will include time-locked video recordings and electroencephalography using a specialized net of 128 electrodes (Electrical Geodesics Inc., EGI; Eugene, OR). Behavioral and cortical responses will be then be analyzed in a blinded fashion to determine the efficacy of the vibratory intervention, as well as to validate what behavioral responses are most correlated with nociception-specific cortical activity.
Interventions
DEVICEBaby GentleStick
The Baby GentleStick is a handheld device that fits and provides vibration to an Owen Mumford Unistik3 Dual lancet. The gentle vibration occurs at 178 Hertz with a free-hanging 0.24 mm range of motion. The device may provide vibration alone and also allow for simultaneous vibration and deployment of the lancet.
Sponsors
Lance M Relland, MD, PhD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
Personnel who code the video recording for behavioral measures and analysis of the electroencephalographic readings will be done in a blinded and/or independent fashion.
Eligibility
Sex/Gender
ALL
Age
36 Weeks to 56 Weeks
Healthy volunteers
Yes
Inclusion criteria
* Neonatal Intensive Care Unit patient * Between 36 to 56 weeks post-menstrual age * Medically stable * Due to have a clinically required bedside heel stick as part of their routine care
Exclusion criteria
* Congenital anomalies or abnormalities affecting the brain * Patient is over 4 months corrected age * Infants who receive analgesics or sedatives within 72 hours prior to assessment * Administration of maternal analgesics or sedatives to which the infant may be exposed
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Nociception-specific Brain Activity | EEG-based responses are very brief, so the relevant assessment window is 350-700 ms after stimulus | Electroencephalography (EEG)-based measurements will be done to detect changes in nociception-specific cortical activity. Recordings will be done using a high-density array of 128 electrodes embedded in soft sponges (Electrical Geodesics, Inc. (EGI); Eugene, Oregon, USA) soaked in warm saline and applied to the infant's head to record event-related potentials (ERPs) with a sampling rate of 1000 Hz, filters set to 0.1-400 Hz. As per published protocols, the midline Cz electrode will be used as the reference. Previous studies have also determined the EEG-based nociception-specific response to occur 350-700 ms after the stimulus. Changes in the amplitude of the signal during this time frame is the primary outcome measure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Facial Expression | Assessment of facial expression is done based on video clips that are synchronized with the ERP window of 350-700ms after stimulus | Components from the Neonatal Facial Coding System (NFCS) use facial actions to monitor pain in newborn infants. Facial actions that occur each score 1 point, while those that do not occur each score 0 points (better outcome). This study applied 7 facial actions and may therefore score between 0 and 7. A higher score (worse outcome) is interpreted as a higher pain intensity. Comparison of median scores between groups will determine the effect of the intervention, which should result in a lower score to represent mitigation of pain. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| No Vibratory Stimulus Before or During Heel Lance Baseline measurements and readings after vibration alone will be done, but no vibratory stimulus will be provided immediately preceding or during heel lance. | 67 |
| Vibratory Stimulus Before and During Heel Lance Baseline measurements and readings after vibration alone will be done, as well as a vibratory stimulus that will be provided immediately preceding and during heel lance.
Baby GentleStick: The Baby GentleStick is a handheld device that fits and provides vibration to an Owen Mumford Unistik3 Dual lancet. The gentle vibration occurs at 178 Hertz with a free-hanging 0.24 mm range of motion. The device may provide vibration alone and also allow for simultaneous vibration and deployment of the lancet. | 67 |
| Total | 134 |
Baseline characteristics
| Characteristic | No Vibratory Stimulus Before or During Heel Lance | Vibratory Stimulus Before and During Heel Lance | Total |
|---|---|---|---|
| Age, Continuous | 39.5 weeks | 39.1 weeks | 39.4 weeks |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 40 Participants | 40 Participants | 80 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Facial Score | 0 units on a scale | 0 units on a scale | 0 units on a scale |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 3 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 6 Participants | 5 Participants | 11 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 29 Participants | 31 Participants | 60 Participants |
| Region of Enrollment United States | 40 participants | 41 participants | 81 participants |
| Sex: Female, Male Female | 17 Participants | 14 Participants | 31 Participants |
| Sex: Female, Male Male | 23 Participants | 27 Participants | 50 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 67 | 0 / 67 |
| other Total, other adverse events | 0 / 67 | 0 / 67 |
| serious Total, serious adverse events | 0 / 67 | 0 / 67 |
Outcome results
Primary
Change in Nociception-specific Brain Activity
Electroencephalography (EEG)-based measurements will be done to detect changes in nociception-specific cortical activity. Recordings will be done using a high-density array of 128 electrodes embedded in soft sponges (Electrical Geodesics, Inc. (EGI); Eugene, Oregon, USA) soaked in warm saline and applied to the infant's head to record event-related potentials (ERPs) with a sampling rate of 1000 Hz, filters set to 0.1-400 Hz. As per published protocols, the midline Cz electrode will be used as the reference. Previous studies have also determined the EEG-based nociception-specific response to occur 350-700 ms after the stimulus. Changes in the amplitude of the signal during this time frame is the primary outcome measure.
Time frame: EEG-based responses are very brief, so the relevant assessment window is 350-700 ms after stimulus
Population: Subjects who had usable, artifact-free EEG data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| No Vibratory Stimulus Before or During Heel Lance | Change in Nociception-specific Brain Activity | Frontal | 17.9 microvolts*milliseconds | Standard Deviation 39.5 |
| No Vibratory Stimulus Before or During Heel Lance | Change in Nociception-specific Brain Activity | Central | 11.5 microvolts*milliseconds | Standard Deviation 12.1 |
| No Vibratory Stimulus Before or During Heel Lance | Change in Nociception-specific Brain Activity | Central Parietal | 12.2 microvolts*milliseconds | Standard Deviation 15.4 |
| Vibratory Stimulus Before and During Heel Lance | Change in Nociception-specific Brain Activity | Frontal | 9.9 microvolts*milliseconds | Standard Deviation 17.1 |
| Vibratory Stimulus Before and During Heel Lance | Change in Nociception-specific Brain Activity | Central | 10.2 microvolts*milliseconds | Standard Deviation 6.8 |
| Vibratory Stimulus Before and During Heel Lance | Change in Nociception-specific Brain Activity | Central Parietal | 12.0 microvolts*milliseconds | Standard Deviation 12.4 |
p-value: <0.001ANCOVA
Secondary
Change in Facial Expression
Components from the Neonatal Facial Coding System (NFCS) use facial actions to monitor pain in newborn infants. Facial actions that occur each score 1 point, while those that do not occur each score 0 points (better outcome). This study applied 7 facial actions and may therefore score between 0 and 7. A higher score (worse outcome) is interpreted as a higher pain intensity. Comparison of median scores between groups will determine the effect of the intervention, which should result in a lower score to represent mitigation of pain.
Time frame: Assessment of facial expression is done based on video clips that are synchronized with the ERP window of 350-700ms after stimulus
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| No Vibratory Stimulus Before or During Heel Lance | Change in Facial Expression | 4 units on a scale |
| Vibratory Stimulus Before and During Heel Lance | Change in Facial Expression | 4 units on a scale |
p-value: 0.38Wilcoxon (Mann-Whitney)