Auricular Acupressure as an Adjunct Treatment for Opioid Tapering in a Pediatric Cardiac Intensive Care Unit: A Pilot Feasibility Study
Phase: NA
Conditions: Iatrogenic Withdrawal Syndrome
Sponsor: Vanderbilt University Medical Center

 
 
 
 
1 
 
 
 
 
 
 
 
 
 
Auricular Acupressure as an Adjunct Treatment for Opioid Tapering 
in a Pediatric Cardiac Intensive Care Unit: A Pilot Feasibility Study 
 
 
PI: Heather Jackson, PhD, APRN, FNP-BC, NEA-BC, ADS 
Michelle Terrell, DNP, APRN, CPNP-AC/PC 
Mary Dietrich, PhD, MS 
Gloria Rubadeau, MSN, APRN, NNP-BC 
Micaela Arseneau, DNP, APRN, CPNP-AC 
Kim Steason, DNP, CPNP-PC/AC  
Ann Sweeney, MD 
 
 
 
 
Protocol version 3/22/22 
NCT05025384 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
2 
 
 
 
 
 
 
Table of Contents: 
 
Study Overview 
1.0 
Background 
2.0 
Rationale and Specific Aims 
3.0 
Animal Studies and Previous Human Studies 
4.0 
Inclusion/Exclusion Criteria 
5.0 
Enrollment/Randomization 
6.0 
Study Procedures 
7.0 
Risks of Investigational Agents/Devices (side effects) 
8.0 
Reporting of Adverse Events or Unanticipated Problems involving Risk to 
Participants or Others 
9.0 
Study Withdrawal/Discontinuation 
10.0 
Statistical Considerations 
11.0 
Privacy/Confidentiality Issues 
12.0 
Follow-up and Record Retention 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
3 
 
 
 
 
 
 
Study Overview 
This intervention pilot feasibility study will assess the impact of auricular acupressure 
as an additional non-pharmacologic therapy for infants at risk for developing Iatrogenic 
Withdrawal Syndrome (IWS) in the Pediatric Cardiac Intensive Care Unit (PCICU) of Monroe 
Carrell Jr Children’s Hospital at Vanderbilt (MCJCHV). We will recruit 40 healthy, 34 weeks 
gestational age or older infants exposed to prolonged medications (greater than 5 days) for 
cardiac procedures that may cause withdrawal upon cessation such as opioids, 
benzodiazepines, or other sedative medications. Participants will receive the auricular 
acupressure in addition to the standard of care such as clustered nursing care, touch, position 
change, environmental controls, holding, and swaddling. Within 24 hours of implementing a 
weaning protocol, acupressure will be applied to three designated points of one ear following 
the NADA protocol acupuncture technique while also incorporating the Near-Term Infant (NTI) 
conceptual framework identified elements (see figure 3). Acupressure will be administered via 
stickers that are adhesive to the skin like a Band-Aid (see figure 1). These stickers include a 
vaccaria plant seed in the center that applies continuous light pressure on the designated 
points. This form of acupressure was selected as it is organic and does not contain metal which 
may interfere with emergency medical care such as imaging. After the initial 24 hours of 
application, stickers will be removed, the infant’s skin will be assessed for any disruption such 
as bruising or discoloration, and the stickers will be rotated to the infant’s other ear at the same 
NADA protocol auricular sites. Acupressure stickers will be removed and applied to the opposite 
ear every 48-72 hours until withdrawal symptoms improve (1). Withdrawal symptoms are 
measured every 6 hours with the enhanced Withdrawal Assessment tool (WAT) as part of the 
standard of care.  Upon completion of the weaning regimen, infants with a score of less than or 
equal to 3 or less than 2 above baseline with no more than 2 rescue medication doses in 24 
hours will have the acupressure removed.  
 
Figure 1: Auricular Acupressure to NADA Protocol Sites 
Acupressure Sticker 
Auricular Application 
NADA Protocol Points: 
Shen Men, Liver, Lung 
 
 
 
 
 

 
 
 
 
4 
 
1.0 
Background 
 
Opioid and benzodiazepine medications are necessitated in the treatment of critically ill 
infants in the cardiac intensive care unit to provide pain relief and anxiolysis. However, use of 
these modalities are associated with a multitude of uncomfortable symptoms surrounding 
physical dependence and may lead to withdrawal syndrome, bowel dysfunction, as well as 
exacerbation of delirium (2). Additionally, long term use of opioids and benzodiazepines in the 
infant population may impair neurodevelopment (3-5). This is especially concerning for infants 
undergoing cardiopulmonary bypass as this intervention further places this population at risk for 
impaired neurological development (6). These medications further contribute to prolonged 
hospital stays as they must be gradually weaned (7, 8).  
Given the sequelae of the prolonged opioid and benzodiazepine exposure in this 
vulnerable population, first line treatments involve the maximization of non-pharmacologic 
therapies. These treatments include swaddling, reduction in environmental stimulation, use of 
sound machines or music, vibration, and soothing touch (9, 10). Yet, these treatments are not 
always successful in significantly reducing symptoms of withdrawal (with significance referring 
to reductions that do not require additional medication administrations).  
The NADA protocol uses an auricular acupuncture technique created by a physician for 
the treatment of addiction and has demonstrated efficacy in the adult population (11-13). 
Acupuncture and acupressure studies in pediatric populations have also demonstrated 
improvement in multiple symptoms commonly experienced by infants in withdrawal. These 
symptoms include pain, agitation, crying, feeding difficulties with subsequent growth impairment, 
and sleep disturbance (14-25). Current evidence suggests acupuncture and acupressure are 
safe on neonates, but high quality randomized controlled trials are needed to confirm efficacy 
for the treatment of withdrawal (1, 23-28). This study, with the use of the NTI, will establish 
efficacy and provide a framework to guide future acupuncture and acupressure studies. 
 
2.0 
Rationale and Specific Aims 
 Sedative medications such as opioids and benzodiazepines are commonly administered 
to improve comfort of infants undergoing cardiac surgical procedures. Unfortunately cessation of 
these medications are commonly associated with onset of uncomfortable withdrawal as infants 
become physically dependent on these medications (29, 30). This condition is known as 
Iatrogenic Withdrawal Syndrome (IWS) and is further associated with impaired neurological 
development as well as prolonged mechanical ventilation and hospital stays (3-5, 31-33). 
Infants with IWS experience a multitude of symptoms shared by other infant conditions 
that have been improved with acupuncture including tremors, hypertonicity, agitation, disrupted 
sleep, feeding difficulty, vomiting, diarrhea, temperature instability, tachypnea, and impaired 
weight gain (34-37). Treatments focus on non-pharmacologic adjuncts that support physiologic 
stability and prevent further developmental difficulties, prolonged hospital stays, and interrupted 
maternal bonding (9, 38, 39). These therapies include swaddling, position change, soothing 
touch, and environmental controls; however, they have not traditionally included acupressure as 
a non-pharmacologic adjunct. Although standard interventions are helpful, there remains a need 
to optimize these interventions and further reduce or prevent the use of medication.  
Current evidence suggests that acupuncture is safe and beneficial for multiple conditions 
that impact neonatal and pediatric populations including withdrawal, yet this therapy remains 
underutilized as there is a lack of high-quality studies evaluating feasibility and therapeutic 
efficacy in the treatment of dependence (1,10-24). A less invasive acupuncture therapy is 
acupressure, a technique that applies mild pressure via stickers, similar to Band-Aids, to 
designated body points rather than needle insertion to provide a therapeutic benefit. 
Acupressure may serve as an additional non-pharmacological adjunct to ease the severe 
discomfort of withdrawal in infants physically dependent on medications. 

 
 
 
 
5 
 
In addition to therapeutic utility of acupressure, it may be cost effective by decreasing 
hospital stays and the need for more expensive and invasive pharmacologic interventions (9). In 
this pilot feasibility study, acupressure will be used as an additional intervention to 
current, standard therapies. The Near-Term Infant conceptual framework (NTI) guided the 
creation of our acupressure protocol to ensure incorporation of standard of care as well as 
optimization of acupressure elements to produce healthy outcomes in infants at risk for 
developing iatrogenic withdrawal syndrome. This acupressure protocol has been implemented 
at MCJCHV in the neonatal abstinence syndrome (NAS) population and was deemed feasible, 
accepted by healthcare providers and mothers, as well as safe. If proven feasible and beneficial 
within a PCICU population, further studies may be conducted to evaluate the efficacy of 
acupressure in easing with withdrawal symptoms as measured by the enhanced withdrawal 
assessment tool (WAT-1), when applied in conjunction with standard treatments.  
Aim 1: Assess feasibility of delivering an acupressure protocol for the treatment of withdrawal in 
a pediatric cardiac intensive care unit. Feasibility will be assessed with successful completion of 
the following objectives: 
a. Achieve recruitment and consent of 4 parents per month whose infant has been 
exposed to opioids and/or benzodiazepines for greater than 5 days, with a retention 
of 80% or higher during a 24 month time period (n=40). 
b. Deliver the acupressure protocol to 20 infants at risk for developing withdrawal within 
the standard of care as an additional non-pharmacologic intervention (20 infants will 
receive standard of care). 
Aim 2: Assess impact of auricular acupressure on withdrawal symptoms for an infant physically 
dependent on opioid and/or benzodiazepine medications. Efficacy of auricular acupressure will 
be assessed, in line with the standard of care, with comparison of the following assessments 
among intervention and control groups: 
a. Duration of opioid and/or benzodiazepine exposure 
b. Duration of wean phase 
c. Duration of mechanical ventilation 
d. Total medication dosage as measured in morphine equivalents and benzodiazepine 
dosages (mg/kg/patient) 
e. Hospital length of stay 
f. Severity of withdrawal symptoms as measured by the Enhanced Withdrawal 
Assessment Tool (WAT-1)  
g. Presence and/or severity of delirium as measured by the Pediatric Confusion 
Assessment Method for the Intensive Care Unit (psCAM-ICU)  
h. Severity of agitation as measured by the Richmond Agitation Sedation Scale (RASS)  
i. 
Infant Pain scores as measured by Faces, Leg, Activity, Cry, Consolability Scale 
(FLACC)   
Aim 3: Assess acceptability and implementation of the acupressure protocol as an adjunct 
treatment for withdrawal syndrome within the standard of care. 
a. Examine parental satisfaction of acupressure as an additional treatment as 
measured by the Client Satisfaction Questionnaire (CSQ8). 
b. Assess provider and staff satisfaction of acupressure as an additional therapy as 
measured by Acceptability of Intervention Measure (AIM), Intervention 
Appropriateness Measure (IAM), and Feasibility of Intervention Measure (FIM). 
c. Assess qualitative feedback as reported by parents and healthcare providers.   
Impact: Results from this proposed study may expand first line, non-pharmacological therapy 
for infants experiencing withdrawal symptoms. Offering enhanced care for IWS infants while 
reducing costs related to hospital treatments is a public health concern during an opioid 
epidemic. Acupressure is safe, noninvasive, inexpensive, and efficiently implemented for 

 
 
 
 
6 
 
disorders with similar conditions to withdrawal syndrome, thus warranting additional 
investigation for consideration as an included standard of practice for post procedural infants. 
 
3.0 
Animal Studies and Previous Human Studies 
 
There is a multitude of research, which has demonstrated efficacy and safety of 
acupuncture and acupressure in the neonatal and pediatric population; including research within 
MCJCHV by the PI yielding no adverse outcomes (28). This treatment has also exhibited 
therapeutic results in veterinary medicine (40).  In pediatrics, acupuncture has demonstrated 
improved myofascial pain and postoperative nausea/vomiting (41, 42). For infants, acupuncture 
and acupressure has reduced crying in infants with colic and reduced pain during procedures 
(14, 19, 22, 43). Incidentally, these positive effects can lead to better attachment with mothers. 
Several studies have outlined the presence of active ear points in the neonate which propose 
the use of auricular acupuncture or acupressure should be considered as an adjunct treatment 
(44-47). More specific research studies in NAS reveal acupuncture and acupressure are 
practical non-pharmacologic interventions (1, 9). Laser acupuncture has been performed on 
infants with NAS and resulted in reduction in morphine use, diarrhea, length of stay and 
improved feeding as well as sleep (23-25). Acupressure in combination with massage has also 
demonstrated efficacy in premature infants weight gain (21). Acupressure is the least invasive 
technique and very well tolerated (48). A similar study performed acupressure on NAS infants in 
1992-1996 with several limitations but there were no adverse reactions or skin disruption noted 
(1). In this study, ear seeds were left in place for up to 72 hours, following the NADA protocol 
without any negative effects. Limitations included lack of control for additional acupressure 
applied by mothers, lack of blinding (sham), and timely application of the seeds (within 24 hours 
of birth).  
 
4.0 
Inclusion/Exclusion Criteria 
 
This prospective pilot study will be conducted over a 24-month period and will enroll a 
total of 40 infants. Infants will be randomized in a 1:1 ratio to the two groups; randomization will 
occur within REDCap. Inclusion criteria are as follows: infants, 34 weeks or greater gestation, 
exposure to opioids and/or benzodiazepine medications for 5 days or more, beginning a stable 
wean, and maternal age of 18 or older as these individuals are able to consent for themselves 
(see Table 2). Exclusion criteria will be captured in the medical record as follows: hemodynamic 
instability, transfer to another facility prior to completion of the weaning regimen or death. 
Parents identified by health care providers in the PCICU will be approached by study providers 
(Jackson, Terrell, Sweeney, Weber, or Williams) in the PCICU. Project procedures will be 
described and if participants would like to enroll in the study, the consent process will be 
completed by study providers. Following informed consent, acupressure will be administered 
within 24 hours MCJCHV. Healthcare providers caring for these infants will be identified through 
the medical record and subsequent surveys sent through their VUMC email. No ethnic group 
will be targeted or excluded from this study. 
 
 
Table 2: Inclusion and Exclusion Criteria 
Inclusion 
Exclusion 
34 weeks gestational age to 1 year of age 
Transfer to another facility prior to wean 
completion  
Maternal age 18 or older 
Re-escalation of care/Worsening Illness 
English speaking 
Death 
Hemodynamically stable 

 
 
 
 
7 
 
Exposure to opioid and/or benzodiazepine for 
5 days or more 
 
5.0 
Enrollment 
A purposeful sampling technique will be utilized to recruit participants from MCJCHV as 
referred by healthcare providers caring for infants exposed to opioids and/or benzodiazepines 
for surgical procedures. Informational flyers (Appendix A) will be produced and provided by 
healthcare providers to parents interested in participating in the study and asked if they would 
like to be contacted by the PI or research team. At that time, parents may contact the PI, ask the 
PI to call them, or the PI will be available during the week (Monday-Friday) to discuss the study 
immediately following their discussion with their healthcare provider. Additionally, infants at risk 
for developing withdrawal may be identified by following the census in the PCICU. Daily 
monitoring of the PCICU census via the electronic medical record will be performed by the PI.  
Previous infant studies, including a pilot feasibility study conducted by the PI at 
MCJCHV, have reported high retention rates of mother’s that consent to acupuncture for the 
treatment of withdrawal but we are mindful of challenges in enrollment and retention (1, 23, 24, 
28). Enrolled participants will remain in the study until cessation of opioid and/or benzodiazepine 
unless they are transferred to another facility (see Table 2 Exclusion Criteria) or parents 
voluntarily withdrawal. If an infant is transferred, acupressure will not be continued but surveys 
will be provided to assess satisfaction and acceptability (Aim 3). Healthcare providers will be 
identified through the medical record and surveys sent through their VUMC email. 
6.0 
Study Procedures (Design) 
6.1. Interventions.  
Acupressure Administration (Aim1). All participants will receive the standard non-
pharmacological treatment, which may include any variety of the following treatments: rooming 
in, soothing tough, swaddling, skin to skin, positioning, reduced stimulation, and sound 
machines, as needed and tolerated. These treatments are documented by nurses in the medical 
record. The essential characteristics for neonatal acupuncture (Figure 3) as guided by the Near-
Term Infant conceptual framework (Figure 2) are included in the delivery of this acupressure 
protocol.  
Within 24 hours of weaning medications, one of five specialty trained advanced practice 
providers will apply acupressure stickers to one ear (left or right depending on access to site) in 
accordance with the NADA protocol acupuncture technique. Application will occur at designated 
points including Shen Men, Liver, and Lung: in the room with the mother; and potentially during 
breast feeding, holding, skin to skin contact or bottle feeds. Administrators and nurses will 
document the activities of the infant during acupressure placement in the medical record. 
Stickers will remain in place for 24 hours.  
At 24 hours, skin will be assessed, and stickers will then be rotated to the opposite ear 
every 48-72 hours if there are no adverse effects such as skin irritation. Should skin irritation be 
present after the 24-hour period, the sticker applied to the opposing ear will be removed in 12 
hours and skin assessed. If skin irritation continues, acupressure will be discontinued, and the 
participant will be withdrawn from the intervention portion of the study. Parents and health care 
providers of the infant will still be provided surveys to assess satisfaction and acceptability of 
acupressure. If no skin irritation occurs, stickers may be rotated for these participants every 12 
hours. Assessment of the ear skin will be documented at the time of acupressure removal in the 
medical record. In accordance with previous neonatal studies that applied auricular acupressure 
under these guidelines (48-72 hour acupressure placement), we do not anticipate skin irritation 
but will continue to monitor throughout hospitalization (1, 20, 28). Acupressure will be 
discontinued when withdrawal symptoms measure less than or equal to 3 or less than 2 above 
baseline with no more than 2 rescue medication doses in 24 hours. Study participants will 

 
 
 
 
8 
 
receive the same assessments as non-participants and must meet the same weaning 
qualifications in line with the standard of care.  
Acupressure Efficacy (Aim 2). As part of the standard of care, multiple metrics will be 
captured and compared among the intervention and control group. These include duration of 
opioid and/or benzodiazepine medications, duration of weaning phase, duration of mechanical 
ventilation, and hospital length of stay. To ensure appropriate opioid dosage comparisons, all 
opioid medications will be converted to morphine equivalents (mg/kg/patient); benzodiazepine 
medications and dosages will also be captured. Consistent with the current standard of care for 
infants treated in the PCICU the following assessments will be conducted: Withdrawal 
Assessment Tool (WAT-1) for Pediatric Withdrawal every 6 hours, Preschool Confusion 
Assessment Method for the ICU (psCAM-ICU) every 12 hours, Richmond Agitation-Sedation 
Scale (RASS) every 2-4 hours and Faces Legs Activity Cry Consolability Scale (FLACC) every 
4 hours.  
Acupressure Acceptability (Aim 3). Prior to discharge and after completion of the 
weaning protocol, parent(s) will receive the Client Satisfaction Questionnaire (CSQ8) to assess 
parental satisfaction of acupressure as an additional therapy. Staff and providers who cared for 
participants will also receive three brief electronic surveys via REDCap directly to their email 
prior to discharge. This survey will include 12 questions: Acceptability of Intervention Measure 
(AIM), Intervention Appropriateness Measure (IAM), and Feasibility of Intervention Measure 
(FIM) to evaluate acceptability of acupressure as a complementary therapy. Qualitative 
feedback back from healthcare providers and parents will be documented by administrators at 
time of acupressure application and skin assessment. Such feedback would include 
observations reported to the research team by healthcare providers or parents. 
6.2. Conceptual Framework & Innovation. An important innovation of this study is the 
development of a standardized protocol specific for infants that is guided by the Near-Term 
Infant (NTI) conceptual framework to ensure that essential components of infant care are 
incorporated in this adjunctive treatment within the standard of care (49). To our knowledge, the 
use of a conceptual framework has only been implemented in one neonatal acupressure study 
(performed by the PI) and no consistent framework has been outlined for future studies. Use of 
the NTI guided the development of our acupressure protocol to ensure optimal delivery of this 
therapy as a complementary treatment for IWS. Based on previous evidence related to 
acceptability of acupressure with neonates, we will eliminate a treatment room during 
application, allowing the infant to be with his/her parents. An auricular technique is supported by 
the NTI to improve physiologic symptoms within the standard of care by reducing stimulation to 
the infant, as full body administration would require unwrapping, exposing body points, and 
laying the infant down. All of the elements defined by the NTI ensure maternal-infant bonding, 
as well as incorporation of family and other human interactions. These are novel elements the 
NADA protocol did not consider as it was developed for the adult population. Use of the NTI is 
innovative and significant in our study as it ensures adaptations to the NADA protocol including 
evidence-based strategies of acupressure that are imperative for the IWS population. 
Cumulatively, these considerations allow for the inclusion of acupressure within the standard of 
care for infants thereby promoting future feasibility and acceptance of this novel treatment by 
parents, health care providers, and institutions.  
 

 
 
 
 
9 
 
FIGURE 2: Near-Term Infant Conceptual 
Framework  
FIGURE 3: Essential Characteristics for Neonatal 
Acupuncture as Informed by the Near-Term Infant 
Conceptual Framework 
 
7.0 
Risks to Participants 
 
This study includes an intervention trial that requires registry in ClinicalTrials.gov. There 
is minimal risk to human participants in the proposed study; nonetheless, rigorous efforts will be 
made to protect them. We will recruit a total of 40 infants at risk for experiencing withdrawal at 
Monroe Carrell Jr. Children’s Hospital at Vanderbilt in Nashville, TN. Recruitment and consent 
will be conducted by the PI and research team. Written, electronic, or telephone  informed 
consent will be obtained prior to initiating any study activities. All key personnel and study team 
members are licensed healthcare professionals with extensive substance dependence and 
neonatal experience that have been specially trained and credentialed to apply auricular 
acupressure.  
The only known physical risk associated with auricular acupressure is the possibility of 
irritation to the infant’s skin such as bruising or discoloration. Skin irritation will be defined as 
bruising, and severe redness as documented by the acupressure provider. Should skin irritation 
be present after the 24-hour period of acupressure application, the sticker applied to the 
opposing ear will be removed in 12 hours (as this is half the initial evaluation period designated 
in the protocol) and skin assessed. If skin irritation occurs in the opposing ear, acupressure will 
be discontinued, and the participant will be withdrawn from the study. If no skin irritation occurs, 
stickers will be rotated for these participants every 12 hours. In accordance with previous 
neonatal studies, including one performed by the PI at MCJCHV, we do not anticipate skin 
irritation when applying auricular acupressure under these guidelines (48-72 hour acupressure 
placement) (1, 20, 28).  
Protections for Infants. Infants in this study will be viable near term gestational age; 
individuals engaged in this research will have no part in determining viability of the neonate. 
Clinical studies have been conducted on the use of acupressure and (more invasive) 
acupuncture and provide data for assessing potential risks to infants. Every parent providing 
consent in this study will be fully informed regarding the reasonably foreseeable impact of 
acupressure in infants experiencing withdrawal from substances.  
Adequacy of Protection Against Risks. All members of the team will have the required 
human participants research (CITI research ethics and compliance) and HIPPA training. All 
paper copies of data will be kept in a locked file cabinet in the PI’s office at VUMC. Electronic 

 
 
 
 
10 
 
information will remain in the password protected, project number identification, REDCap 
database. The PI and research team will always be available to the healthcare providers and 
staff via cell phone. Participants’ parents will be given a telephone number, pager number, and 
email address which will allow them to contact the PI at any time. Should there be any adverse 
events, PCICU providers are available to provide care for the infants.  
Potential Benefits of the Proposed Research to Participants. Acupressure may serve as 
an additional non-pharmacologic intervention that improves symptoms of withdrawal in infants at 
risk of developing withdrawal syndrome. In addition to therapeutic utility of acupressure, it may 
be cost effective by decreasing hospital stays as well as the need for more expensive and 
invasive pharmacologic interventions. 
Importance of the Knowledge to be Gained. Acupressure may augment current first line 
therapies assisting in the avoidance of medications, promoting maternal bonding, and reducing 
hospital length of stay. If proven feasible within a pediatric cardiac intensive care population, 
further studies may be conducted to evaluate the efficacy of acupressure in easing withdrawal 
symptoms as measured by the enhanced Withdrawal Assessment Tool (WAT), when applied in 
conjunction with standard treatments.  
Data and Safety Monitoring Plan. The PI is responsible for the monitoring of the 
progress of the study and safety of all participants. Participants must meet all inclusion criteria 
and none of the exclusion criteria. All discussions with participants’ parents will take place in 
confidential areas (private room or hospital room inpatient).  
 
8.0 
Reporting of Adverse Events or Unanticipated Problems involving Risk to 
Participants or Others 
 
The study team is comprised of seven specialty trained and credentialed providers that 
will communicate any issues such as skin irritation to the PI immediately. Adverse events (AE) 
in this study will be minimal as there are no invasive procedures and the intervention may be 
administered within the standard of care as the PI has done previously at MCJCHV; with no 
reported AE (28). However, AE will be monitored throughout the study and any event will be 
followed to resolution or stabilization. An AE is defined as any unfavorable medical occurrence 
in a human study participant, whether or not it is considered to be related to participation in the 
research. Any AE will be reported to the VUMC IRB immediately. An unanticipated problem 
(UP) is any incident, experience, or outcome that meets all of the following criteria: a) 
unexpected given the research procedures and characteristics of the study population, b) 
related or possibly related to participation in the research and c) suggests that the research 
places participants or others at a greater risk of harm than was previously known or recognized. 
We will report any such events to the IRB. The PI will provide continuous, close monitoring of 
participants at VUMC with prompt reporting of AEs to the IRB and will follow VUMC reporting 
guidelines. 
 
9.0 
Study Withdrawal/Discontinuation 
 
Participants may withdraw from the study at any time and continue standard care. 
Participants may be withdrawn if deemed medically necessary by an attending physician or 
study staff or if exclusion criteria are met. Participants may be withdrawn from the study by the 
principal investigator for repeated non-compliance. This would entail altering the seed 
placement for example. Participants will be reminded that participation will not affect their 
clinical services and the CSQ8 parental satisfaction survey will be provided to parents of 
participants.  
 
10.0 
Statistical Considerations: Analysis Plan 

 
 
 
 
11 
 
The study sample will be characterized using descriptive statistics including 
mean/median, standard deviations/interquartile range, proportions and percentages as outlined 
below. Benchmarks for success are summarized in Table 2.  
Data Analysis Aim 1. The primary goal of this aim is to assess feasibility and 
implementation of this study including recruitment, retention, and execution of and adherence to 
the acupressure protocol. Feasibility measures will be reported as frequencies and proportions 
(% of eligible patients enrolled, % of patients prematurely terminating treatment, % of patients 
completing all study assessments, % of data collection procedures completed, % of missing 
medical record data). Feasibility will be determined through the following benchmarks: a) 
recruitment success: recruitment rate of 2 infants per month over the proposed 24-month time 
frame (80% of 40 (ex 32) enrolled); b) study retention: retention of >80% of participants through 
all assessment periods, c) adherence to the acupressure administration protocol: advanced 
practice providers will record at least 90% of all acupressure sessions in the REDCap database 
and medical record.   
Data Analysis Aim 2. Descriptive data will be generated for the outcomes detailed in 
Table 2: Aim 2 by treatment group. Given the feasibility goal of this study, we will not conduct 
formal statistical tests of association between the two treatment groups, but we will provide 
descriptives by groups and measures of variability. These statistics will inform us of data trends. 
Descriptives will be generated based on the intent to treat principle.  
 
Data Analysis Aim 3. Parental satisfaction with acupressure as an additional non-
pharmacologic intervention will be reported as means with standard deviations and percentiles 
of the CSQ8 scores within each category of the following: excellent, good, fair and poor. 
Provider and staff acceptability of acupressure as an additional non-pharmacologic treatment 
will be measured with the Acceptability of Intervention Measure (AIM), Intervention 
Appropriateness Measure (IAM), and Feasibility of Intervention Measure (FIM). These 
measures will be reported as frequency distributions and proportions (% of AIM scores, % of 
IAM scores, and % of FIM scores). 
 
Table 2: Assessment Measures  
Outcomes 
Measures 
Time Point 
Aim 1 Feasibility of Acupressure 
Protocol 
 
Demographics: age median & 
interquartile range, weight median & 
interquartile range, % male/female, % 
race (black, white, Hispanic) 
 
 
Recruitment Metrics: % of eligible 
patients enrolled, % of patients 
prematurely terminating treatment, % 
of patients completing all study 
assessments, % of data collection 
procedures completed, % of missing 
medical record data 
 
Enrollment Metrics: % of eligible 
patients enrolled, % of patients 
prematurely terminating treatment, % 
of patients completing all study 
assessments, % of data collection 
procedures completed, % of missing 
medical record data 
 
Duration of study 
 
 
 
 
 
Duration of study 
 
 
 
 
 
 
 
Duration of study  
 
 
 
 
 
 
 

 
 
 
 
12 
 
Acupressure Administration: % sticker 
displacement & reapplication, adverse 
events 
 
Infant Activity, Non-Pharmacologic 
Treatments  
Every 24-72 hours 
 
 
 
Every 6 hours 
Aim 2 Acupressure Efficacy  
 
 
 
Duration of Medication Exposure 
(days): median, interquartile range  
 
Duration of Wean Phase (days): 
median, interquartile range 
 
Duration of Mechanical Ventilation 
(days): median, interquartile range 
 
Total Medication Equivalents 
(mg/kg/pt): median, interquartile range 
 
Hospital Length of Stay (days): 
median, interquartile range 
 
Exposure to adjunct medications: 
median, interquartile range 
 
WAT-1 Scores: median, interquartile 
range 
 
psCAM-ICU Scores: median, 
interquartile range 
 
RASS Scores: median, interquartile 
range 
 
FLACC Scores: median, interquartile 
range 
Duration of study 
 
 
Duration of study 
 
 
Duration of study  
 
 
Every 24 hours  
 
 
Duration of study 
 
 
Every 24 hours 
 
 
Every 6 hours 
 
 
Every 12 hours 
 
 
Every 2-4 hours 
 
 
Every 4 hours 
Aim 3 Acceptability 
Parental Satisfaction: CSQ8 means, 
SD, % scores  
 
Staff/Provider Acceptability: % AIM 
scores, % IAM scores, % FIM scores 
 
Qualitative Feedback 
Duration of study 
 
 
Completion of Study 
 
 
Every 24-72 hours 
 
 
11.0 
Privacy/Confidentiality Issues 
 
There is a risk of breach in confidentially; however, steps will be taken to decrease this 
risk as all data will be collected by the PI from the medical record then input into REDCap. 
Databases will only be accessible by members of the study team, password protected, and a 
confidential project identification number will be assigned. This information will include 
recruitment metrics (Aim 1), and parental satisfaction and acceptability data (Aim 3) including 
the following surveys: CSQ8, AIM, IAM, FIM and qualitative.  

 
 
 
 
13 
 
Recruitment of parents will take place during routine care. Confidentially and privacy will 
be ensured by the PI and healthcare providers when discussing the study and potential 
participation.  
 
12.0 
Follow-up and Record Retention 
 
All data will be stored in the Vanderbilt University Medical Center REDCap. Only 
authorized study personnel will have access to the password protected data tracking system 
and the project will have an identification number assigned. Paper copies of research records 
such as completed paper consent forms and surveys will be kept in a designated binder and 
locked cabinet in a restricted access office at Vanderbilt University Medical Center or uploaded 
into REDCap. The PI will manage data including quality assessment (completeness and 
accuracy) to ensure all variables are captured and entered into REDCap appropriately. At 
completion of the study, the PI will archive paper copies of research records in accordance with 
Vanderbilt University Medical Center’s policy and as recommended by the institutional review 
board (IRB).  
 
13.0 
References 
 
1. 
Schwartz L, Xiao R, Brown E, Sommers E. Auricular acupressure augmentation of 
standard medical management of the neonatal narcotic abstinence syndrome. Medical 
Acupuncture. 2011;23(3):175-86. 
2. 
Amirnovin R, Sanchez-Pinto LN, Okuhara C, Lieu P, Koh JY, Rodgers JW, et al. 
Implementation of a Risk-Stratified Opioid and Benzodiazepine Weaning Protocol in a Pediatric 
Cardiac ICU. Pediatr Crit Care Med. 2018;19(11):1024-32. 
3. 
McPherson C, Inder T. Perinatal and neonatal use of sedation and analgesia. Semin Fetal 
Neonatal Med. 2017;22(5):314-20. 
4. 
Weber F, Van Beek S, Scoones G. Potential neurotoxicity of anesthetic drugs in young 
children: who cares? A survey among European anesthetists. Minerva Anestesiol. 
2016;82(3):294-300. 
5. 
Chen X, Wan Y, Wen K, Liang T, Lin T, Li P. [Perioperative anesthetic exposure and the 
neurodevelopmental status of 1 year old baby underwent neonatal cardiac surgery]. Zhong Nan 
Da Xue Xue Bao Yi Xue Ban. 2015;40(11):1234-8. 
6. 
Mebius MJ, Kooi EMW, Bilardo CM, Bos AF. Brain Injury and Neurodevelopmental 
Outcome in Congenital Heart Disease: A Systematic Review. Pediatrics. 2017;140(1). 
7. 
Barnett AM, Machovec KA, Ames WA, Homi HM, Turi JL, Koo J, et al. The effect of 
intraoperative methadone during pediatric cardiac surgery on postoperative opioid 
requirements. Paediatr Anaesth. 2020. 
8. 
Gupta P, Whiteside W, Sabati A, Tesoro TM, Gossett JM, Tobias JD, et al. Safety and 
efficacy of prolonged dexmedetomidine use in critically ill children with heart disease*. Pediatr 
Crit Care Med. 2012;13(6):660-6. 
9. 
Edwards L, Brown LF. Nonpharmacologic management of neonatal abstinence 
syndrome: an integrative review. Neonatal network : NN. 2016;35(5):305-13. 
10. 
Maguire D. Care of the infant with neonatal abstinence syndrome: strength of the 
evidence. The Journal of perinatal & neonatal nursing. 2014;28(3):204-11; quiz E3-4. 
11. 
Stuyt EB, Voyles CA, Bursac S. NADA Protocol for Behavioral Health. Putting Tools in the 
Hands of Behavioral Health Providers: The Case for Auricular Detoxification Specialists. 
Medicines (Basel, Switzerland). 2018;5(1). 

 
 
 
 
14 
 
12. 
Association NAD. Acupuncture Detoxification Specialist Training and Resource Manual. 
Fourth ed: NADA Literature Clearinghouse; 2015. 203 p. 
13. 
Bergdahl L, Berman AH, Haglund K. Patients' experience of auricular acupuncture during 
protracted withdrawal. Journal of psychiatric and mental health nursing. 2014;21(2):163-9. 
14. 
Landgren K, Kvorning N, Hallstrom I. Acupuncture reduces crying in infants with infantile 
colic: a randomised, controlled, blind clinical study. Acupuncture in medicine : journal of the 
British Medical Acupuncture Society. 2010;28(4):174-9. 
15. 
Gentry KR, McGinn KL, Kundu A, Lynn AM. Acupuncture therapy for infants: a 
preliminary report on reasons for consultation, feasibility, and tolerability. Paediatric 
anaesthesia. 2012;22(7):690-5. 
16. 
Nager AL, Kobylecka M, Pham PK, Johnson L, Gold JI. Effects of acupuncture on pain 
and inflammation in pediatric emergency department patients with acute appendicitis: a pilot 
study. Journal of alternative and complementary medicine (New York, NY). 2015;21(5):269-72. 
17. 
Tsai SL, Reynoso E, Shin DW, Tsung JW. Acupuncture as a Nonpharmacologic 
Treatment for Pain in a Pediatric Emergency Department. Pediatric emergency care. 2018. 
18. 
Yang C, Hao Z, Zhang LL, Guo Q. Efficacy and safety of acupuncture in children: an 
overview of systematic reviews. Pediatric research. 2015;78(2):112-9. 
19. 
Abbasoglu A, Cabioglu MT, Tugcu AU, Ince DA, Tekindal MA, Ecevit A, et al. Acupressure 
at BL60 and K3 Points Before Heel Lancing in Preterm Infants. Explore (New York, NY). 
2015;11(5):363-6. 
20. 
Chen KL, Lindrea KB, Quah-Smith I, Schmolzer GM, Daly M, Schindler T, et al. Magnetic 
noninvasive acupuncture for infant comfort (MAGNIFIC) - a single-blinded randomised 
controlled pilot trial. Acta paediatrica (Oslo, Norway : 1992). 2017;106(11):1780-6. 
21. 
Chen LL, Su YC, Su CH, Lin HC, Kuo HW. Acupressure and meridian massage: combined 
effects on increasing body weight in premature infants. Journal of clinical nursing. 
2008;17(9):1174-81. 
22. 
Ecevit A, Ince DA, Tarcan A, Cabioglu MT, Kurt A. Acupuncture in preterm babies during 
minor painful procedures. Journal of traditional Chinese medicine = Chung i tsa chih ying wen 
pan. 2011;31(4):308-10. 
23. 
Filippelli AC, White LF, Spellman LW, Broderick M, Highfield ES, Sommers E, et al. Non-
Insertive Acupuncture and Neonatal Abstinence Syndrome: A Case Series from an Inner City 
Safety Net Hospital. Global advances in health and medicine : improving healthcare outcomes 
worldwide. 2012;1(4):48-52. 
24. 
Raith W, Schmolzer GM, Resch B, Reiterer F, Avian A, Koestenberger M, et al. Laser 
Acupuncture for Neonatal Abstinence Syndrome: A Randomized Controlled Trial. Pediatrics. 
2015;136(5):876-84. 
25. 
Raith W, Urlesberger B. Laser acupuncture as an adjuvant therapy for a neonate with 
neonatal abstinence syndrome (NAS) due to maternal substitution therapy: additional value of 
acupuncture. Acupuncture in medicine : journal of the British Medical Acupuncture Society. 
2014;32(6):523-4. 
26. 
Jackson HJ, Lopez C, Miller S, Engelhardt B. A Scoping Review of Acupuncture as a 
Potential Intervention for Neonatal Abstinence Syndrome. Med Acupunct. 2019;31(2):69-84. 
27. 
Jackson HJ, Lopez C, Miller S, Englehardt B. Neonatal Abstinence Syndrome: An 
Integrative Review of Neonatal Acupuncture to Inform a Protocol for Adjunctive Treatment. Adv 
Neonatal Care. 2019;19(3):165-78. 
28. 
Jackson HJ, Lopez C, Miller S, Englehardt B. Feasibility of auricular acupressure as an 
adjunct treatment for neonatal opioid withdrawal syndrome (NOWS). Subst Abus. 2020:1-10. 

 
 
 
 
15 
 
29. 
Whelan KT, Heckmann MK, Lincoln PA, Hamilton SM. Pediatric Withdrawal Identification 
and Management. J Pediatr Intensive Care. 2015;4(2):73-8. 
30. 
Fernández-Carrión F, Gaboli M, González-Celador R, Gómez de Quero-Masía P, 
Fernández-de Miguel S, Murga-Herrera V, et al. Withdrawal syndrome in the pediatric intensive 
care unit. Incidence and risk factors. Med Intensiva. 2013;37(2):67-74. 
31. 
Duceppe MA, Perreault MM, Frenette AJ, Burry LD, Rico P, Lavoie A, et al. Frequency, 
risk factors and symptomatology of iatrogenic withdrawal from opioids and benzodiazepines in 
critically Ill neonates, children and adults: A systematic review of clinical studies. J Clin Pharm 
Ther. 2019;44(2):148-56. 
32. 
da Silva PS, Reis ME, Fonseca TS, Fonseca MC. Opioid and Benzodiazepine Withdrawal 
Syndrome in PICU Patients: Which Risk Factors Matter? J Addict Med. 2016;10(2):110-6. 
33. 
Tanaka C, Shimizu N, Staito O, Motomura M, Watanabe I. Risk factor of withdrawal 
syndrome in the paediatric ICU. Critical Care. 2014;18(1):P421. 
34. 
Kraft WK, van den Anker JN. Pharmacologic management of the opioid neonatal 
abstinence syndrome. Pediatric clinics of North America. 2012;59(5):1147-65. 
35. 
Sublett J. Neonatal abstinence syndrome: therapeutic interventions. MCN The American 
journal of maternal child nursing. 2013;38(2):102-7; quiz 7-9. 
36. 
Grim K, Harrison TE, Wilder RT. Management of neonatal abstinence syndrome from 
opioids. Clinics in perinatology. 2013;40(3):509-24. 
37. 
Sutter MB, Leeman L, Hsi A. Neonatal opioid withdrawal syndrome. Obstetrics and 
gynecology clinics of North America. 2014;41(2):317-34. 
38. 
Davis JM, Shenberger J, Terrin N, Breeze JL, Hudak M, Wachman EM, et al. Comparison 
of Safety and Efficacy of Methadone vs Morphine for Treatment of Neonatal Abstinence 
Syndrome: A Randomized Clinical Trial. JAMA pediatrics. 2018;172(8):741-8. 
39. 
Boucher AM. Nonopioid management of neonatal abstinence syndrome. Advances in 
neonatal care : official journal of the National Association of Neonatal Nurses. 2017;17(2):84-
90. 
40. 
Habacher G, Pittler MH, Ernst E. Effectiveness of acupuncture in veterinary medicine: 
systematic review. Journal of veterinary internal medicine. 2006;20(3):480-8. 
41. 
Jindal V, Ge A, Mansky PJ. Safety and efficacy of acupuncture in children: a review of 
the evidence. Journal of pediatric hematology/oncology. 2008;30(6):431-42. 
42. 
Lee A, Fan LT. Stimulation of the wrist acupuncture point P6 for preventing 
postoperative nausea and vomiting. The Cochrane database of systematic reviews. 
2009(2):Cd003281. 
43. 
Reinthal M, Andersson S, Gustafsson M, Plos K, Lund I, Lundeberg T, et al. Effects of 
minimal acupuncture in children with infantile colic - a prospective, quasi-randomised single 
blind controlled trial. Acupuncture in medicine : journal of the British Medical Acupuncture 
Society. 2008;26(3):171-82. 
44. 
Raith W, Pichler G, Zotter H, Mueller W, Urlesberger B. Detection of psychic ear 
acupuncture points in a newborn infant with neonatal abstinence syndrome. Journal of 
alternative and complementary medicine (New York, NY). 2010;16(4):345-6. 
45. 
Kurath-Koller S, Pansy J, Mileder LP, Schmolzer GM, Urlesberger B, Raith W. Active 
Somatic and Psychic Ear Acupuncture Points in Newborn Infants with Neonatal Abstinence 
Syndrome. Journal of alternative and complementary medicine (New York, NY). 
2016;22(10):788-93. 
46. 
Van Amerongen KS, Blattmann FC, Kuhn A, Surbek D, Nelle M. Ear acupuncture points 
in neonates. Journal of alternative and complementary medicine (New York, NY). 
2008;14(1):47-52. 

 
 
 
 
16 
 
47. 
Raith W, Kutschera J, Muller W, Urlesberger B. [Ear acupuncture points in neonates with 
neonatal abstinence syndrome due to maternal substitution therapy]. Zeitschrift fur Geburtshilfe 
und Neonatologie. 2010;214(3):103-7. 
48. 
Yeh ML, Wang PL, Lin JG, Chung ML. The effects and measures of auricular acupressure 
and interactive multimedia for smoking cessation in college students. Evidence-based 
complementary and alternative medicine : eCAM. 2014;2014:898431. 
49. 
Medoff-Cooper B, Bakewell-Sachs S, Buus-Frank ME, Santa-Donato A. The AWHONN 
Near-Term Infant Initiative: a conceptual framework for optimizing health for near-term infants. 
Journal of obstetric, gynecologic, and neonatal nursing : JOGNN / NAACOG. 2005;34(6):666-71.