Clinical trial NCT02456909
Conditions: Postoperative Pain
Sponsor: Medical College of Wisconsin
Start date: 2015-04-01; Completion date: 2019-10-03
Enrollment: 176 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
To examine whether providing patients with a cue to the availability of pain medication affects patient satisfaction, patient anxiety, PCA efficacy, and safety.

Detailed description:
Post-operative pain is primarily managed via Patient-Controlled Analgesia (PCA). The newest PCA pumps can be programmed so that the button is backlit with a green light at the end of the lockout period, and the green light flashes when the medication is being dispensed. No studies have examined whether this type of visual cue would influence satisfaction or other patient outcomes (such as opioid consumption, PCA safety and patient anxiety) in children and adolescents, and no studies have examined whether pediatric patients' perspectives would be similar to those of adults.

Arms: arm 1: The PCA pump will be programmed to provide a cue to the end of the lockout period. arm 2: The PCA pump will be programmed such that no cues will be provided to the end of the lockout period (current standard of care).
Interventions: intervention 1: Patient-Controlled Analgesia pump with Cues intervention 2: Patient-Controlled Analgesia pump without Cues intervention 3: Morphine
Intervention descriptions: intervention 1: The end of the lockout period will be cued via the PCA pump intervention 2: The PCA pump will be programmed such that no cues will be provided to the end of the lockout period. intervention 3: Morphine will be administered for post-operative pain in both the Cues and Non-Cues groups

Protocol documents:
Prot_SAP_000.pdf: 
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Investigating the effects of cuing medication availability on patient-controlled analgesia pump 
usage in pediatric patients: Results of a randomized controlled trial 
 
 
NCT02456909 
 
 
Date of Document:  March 30, 2015 
 
 


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Study Protocol and Statistical Analysis Plan 
Materials and Methods 
This single-center, prospective, RCT was conducted at a large children’s hospital in the 
Midwest. The study was approved by the hospital Institutional Review Board, and was 
registered at www.clinicaltrials.gov (ID: NCT02456909) by the principal investigators prior to 
study enrollment. Enrollment was April 2015 – August 2017. 
 
Participants 
Potential participants between the ages of 7 – 17 years, undergoing an orthopedic, 
abdominal or thoracic surgery for which PCA is routinely prescribed for post-operative pain 
management, were identified from the hospital surgery schedule. Eligible patients were opioid 
naïve, and patients and at least one parent were able to read and speak English. Exclusion 
criteria included 1) prior experience with PCA, 2) cognitive delay precluding independent use of 
the PCA button, or 3) pre-operative use of a daily anxiolytic or antidepressant medication. 
 
Procedures 
Recruitment and Randomization 
Patients were approached immediately prior to surgery. After informed consent and 
assent were obtained, participants were randomized into either the control group or the 
experimental “light” group and were stratified by gender and surgical procedure (orthopedic, 
abdominal, or thoracic) in blocks of 4. The randomization scheme was created by a statistician 
on the research team using Windows version 6.0 of “rand.exe” (http://block-stratified-
randomization.software.informer.com). Participants were enrolled by the clinical research 
coordinator, who used the scheme to assign participants to groups after consent. Recruitment 
continued until each group included 60 completed participants (defined as having completed at 
least 24 hours of PCA use and completed assessment of the primary outcome). Carefusion 


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Alaris™ PCA pumps were used for all patients. The PCA profile (i.e. configuration of the light 
cue operation) for both groups was set up by a nurse in the post-anesthesia care unit (PACU). 
The starting opioid dose is standardized, and was set up by the PACU nurse. For the control 
group, the PCA pump was used according to the hospital’s standard operating procedures: The 
PCA emitted a “beep” with every button press, and the status of the green light on the button 
never changed (i.e., it remained continually lit). For the light group, the PCA pump was 
configured so that the PCA button only emitted a “beep” when a button press resulted in 
successful opioid delivery. The green light on the button flashed during opioid delivery, was 
darkened immediately after delivery and was illuminated at the end of the lockout period, 
indicating a dose was ready to be delivered. Treatment of side effects was determined by the 
floor nurse who was not a member of the study team. To ensure consistent messaging, patients 
and parents in both groups were given scripted instructions regarding PCA use. The patient and 
guardian were also given a printed copy of the instructions prior to surgery. 
 
PCA monitoring and Pain assessments 
Either morphine or hydromorphone (converted to morphine equivalents) was administered using 
PCA for both groups as prescribed by the anesthesia service. Using morphine equivalents, our 
standardized PCA orders are as follows: 20 mcg/kg for the PCA dose and basal (if used), 8 
minute lockout, and a 120 mcg/kg hourly maximum.  
Patients had continuous pulse oximetry.  Pain and sedation scores were recorded every 
2 hours for the first 24 hours, with a minimum of every 4 hours thereafter. PCA use, including 
injections (i.e. button presses resulting in delivered doses) and attempts (i.e. button presses 
during the lockout period), were documented hourly by a nurse who was not a member of the 
study team. If for some reason the nurse was unable to document the hourly number of 


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injections and attempts (e.g. busy with another patient), the following hour’s data would reflect 
the previous 2 hours’ worth of attempts and injections.   
Data collection terminated when the PCA was discontinued, or up to 60 hours post-
surgery, whichever came first. The study period was defined as beginning when the patient 
arrived in the Post-Anesthesia Care Unit (PACU) through Post-Operative Day (POD) 2.  
 
Measures 
All outcomes were collected on post-operative days (PODs) 0-2, with the exception of 
state anxiety on POD 0, which was collected prior to surgery in the pre-op holding area. The 
research coordinator administered the STAI once on each POD, and also extracted all other 
data from the participant’s electronic health record (EHR).  
 
Demographics, anthropometrics, and treatment 
Demographics (age, sex, race and ethnicity) and anthropometrics (height, weight, and 
BMI percentile) were extracted from the EHR. Benzodiazepine (lorazepam, diazepam), 
acetaminophen, ibuprofen, and ketorolac use and intraoperative methadone administration were 
also extracted from the EHR. These data were collapsed across PODs, and reported as 
presence/absence. Pre-existing chronic pain was also extracted from the EHR and reported as 
presence/absence. 
 
Primary Outcome:  Patient satisfaction with pain management 
The primary outcome was the patient’s response to a single question, focused 
specifically on satisfaction with pain management:  “How satisfied were you with your pain 
management (was your pain well controlled)?,” with 0 = “very dissatisfied” and 10 = “very 
satisfied”. Participants answered additional questions to rule out factors that could potentially 
explain between-group similarities or differences in opioid consumption (e.g. Did you 


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understand how to use the pain pump?). These questions were completed independently by the 
patient within 24 hours of the end of the study period. Questions were developed by experts in 
pediatric pain management and were based on the study by Patak et al.1  
 
Secondary Outcomes 
Opioid consumption and opioid-related side-effects 
Data on opioid consumption and treatment of related side effects were extracted from 
the EHR. Total opioid consumed via PCA was calculated from all opioid delivered via the basal 
rate and via injections, and is reported in mg/kg/hr. Hydromorphone was converted to morphine 
equivalents by multiplying the total amount of hydromorphone consumed (mg) by 5.2 
Data on side effects requiring treatment included nausea/vomiting, pruritus, over 
sedation (using the Children’s Hospital of Wisconsin Sedation Scale,3 and respiratory 
depression. Treatment was coded as yes/no for each POD.  
 
Pain intensity 
Pain scores: Pain scores were recorded from the time patients left the PACU until 
discontinuation of the PCA or through POD 2 (whichever came first) and were extracted from 
the EHR. Pain was assessed using the age appropriate, hospital approved pain scale. Children 
either used a 0-10 (0 = no pain, 10 = worst pain possible) numeric rating scale, or the 0-10 
Faces Pain Scale-Revised [10]. 
 
PCA usage 
The total number of hourly injections and attempts were extracted from the EHR.  
 
State Anxiety 


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The Spielberger State-Trait Anxiety Inventory for Children (STAI-C), state version, is a 
well-validated 20 item questionnaire used to assess anxiety about a current situation or 
impending event 4.  Each question begins with the stem “I feel…” and ends with 3 choices (e.g., 
“very calm,” “calm,” “not calm”).  Respondents are instructed to consider “how you feel right 
now.” A total score is computed from a sum of the items, with scores ranging from 0 – 60. The 
STAI-C was administered by the research coordinator once before surgery (POD 0) and once 
per day on POD 1 and POD 2. Elevated state anxiety was based on T-scores and was defined 
as ≥ 1 standard deviation above the mean.5  
 
Power Analysis:  
An a priori sample size calculation was based on the primary outcome. Rahman et al. 
examined patient satisfaction with pain relief for those randomized to pain management with 
PCA vs. intravenous boluses of analgesia titrated to patient comfort levels.6 Based on a 1-5 
scale (1 = excellent, 5 = disappointing), the average pain relief rating for patients in the PCA 
group was significantly better at 2.0 (± 0.37) than the rating for patients in the control group at 
3.0 (± 0.24). With a power of 80%, a type I error rate (alpha) of 0.05, and a two-tailed t test, 60 
patients would have been needed in each group to detect a difference of at least 0.16 SD 
between the light and control groups.  
 
Statistical Analysis 
 
Modified intent-to-treat analyses included all randomized participants, with the exception 
of those who did not receive the allocated intervention, as shown in Figure 1. Means and 
standard deviations or median and interquartile range (IQR) when data were skewed, were 
used for continuous data, and categorical items were described using frequency statistics. A 
Chi-square test or a Fisher’s exact test was used to explore the relations between categorical 
variables, and bivariate correlations (Pearson correlation test) were used to explore correlations 


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between continuous variables. Comparisons between intervention and control groups and 
between age groups [children (12 years) and adolescents (13-17 years)] were conducted using 
a Mann-Whitney test. Missing data were treated using listwise deletion, and assumed to be 
missing completely at random. A two-sided p-value<0.05 was used to define what was 
considered significant. 
Multivariable analyses using a mixed model with random time were used to examine the 
effect of the intervention group and age group on two dependent variables (DV): 1) opioid 
consumption over time and, 2) injections:attempts ratio over time. The independent covariates 
(IV) considered were pain scores, methadone use and the interaction between methadone use 
and intervention group, age group, intervention group, and the interaction between age group 
and intervention group. A backward model selection procedure was used, with a p-value <0.05 
as a criterion to keep the variable in the multivariable model. Based on this criterion, the 
interaction between intraoperative methadone and intervention group was dropped from the 
model. The DV opioid consumption was transformed using square root to satisfy model 
assumptions. The parameters were estimated using Maximum likelihood, and unstructured 
covariance structure was used for repeated measurements. The mixed model with random 
effects allows for missing data, under the assumption that data were missing at random. 
Statistical analyses were calculated using SPSS 24 (IBM SPSS Inc., Chicago, IL) and SAS 9.4 
software (SAS Institute Inc., Cary, NC).