Vibration Analgesia in Propofol Infusion During Anesthesia Induction
Phase: NA
Conditions: Pain, Acute
Sponsor: Montefiore Medical Center

The Effect of Vibration on Pain during Intravenous Injection of Propofol: A Randomized, 
Controlled, Single-blinded Study 
 
Registered United States Food and Drug Administration (FDA) Clinical Trial (NCT #03509857) 
 
Document last updated: February 16, 2022 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Background and Significance  
Infusion of propofol during the process of inducing anesthesia can cause a fair amount of 
transient discomfort to patients while they are on the operating table. It is not uncommon for 
patients to cry out in pain. The investigators have noticed this first hand on numerous occasions 
and have wondered if there is a risk-free way to lesson the pain associated with propofol 
infusion.  
This study will focus on the use of vibration analgesia to potentially reduce the pain associated 
with propofol infusion. Vibration is proposed to stimulate A-beta nerve fibers, which transmit 
information from vibration and touch which, according to the Gate Control Theory of Pain 
(Melzack and Wall 1965), inhibits signal transduction by A-delta and C fibers (Kakigi and 
Shibasaki 1992). Vibration has been demonstrated to be effective in decreasing pain during 
vaccinations, phlebotomy, and dental anesthesia (Baxter et al. 2011; Nanitsos et al. 2009).  
In this study, we seek to evaluate the role of vibration in the reduction of discomfort associated 
with painful stimulus during anesthesia induction. Through this study, we hope to develop a 
comprehensive and cost-effective approach to minimize patient discomfort during anesthesia 
induction.  
Study Design  
The objective of this study is to evaluate the effectiveness of vibration as an analgesic during 
induction of anesthesia. It is our hypothesis that vibration will lessen the pain of propofol 
infusion.  
Patients who are set to receive a propofol infusion as part of induction of general anesthesia 
during surgery will be recruited to participate in this study. All participating patients will be 
randomized following acquisition of consent for study participation to one of two intervention 
groups: 1) normal standard of care infusion of propofol without vibration analgesia 2) infusion of 
propofol with application of vibration analgesia prior to infusion. The amount of pain perceived 
by patients during the infusion will be analyzed via two methods: first the commonly utilized 
visual analogue scale (VAS) as well as the more objective four-point pain manifestation scale 
(J.-R. Lee et al. 2007, Grauers et al. 2002). Patients will be asked to place a mark on a 10-cm 
visual analogue scale corresponding to the level of pain that they experienced during the 
infusion, as commonly utilized in previous studies. Additionally, two trained study investigators 
(one blinded to treatment group) will document the subject's perceived maximum 
pain/discomfort using a four-point pain manifestation scale as outlined in previous pain studies: 
(1) "severe" pain if pain manifests as verbal response accompanied by facial grimacing or 
withdrawal of arm, (2) "moderate" pain if grimacing or arm withdrawal is not accompanied by 
verbal response, (3) "mild" pain if within 30 seconds, severe or moderate pain is not observed, 
the patient is asked whether they had any discomfort in the arms and they answer 'yes,' (4) 
"no"- pain if within 30 seconds, severe or moderate pain is not observed, the patient is asked 
whether they had any discomfort in the arms and they answer 'no.'  
Due to constraints regarding the validity of the linear visual analogue scale in very young 
patients (Stinson et al. 2006), only adults who are able to consent for themselves will be eligible 
for participation in the study.  
Exclusion criteria include minors and pregnant individuals.  

The primary outcome will be the level of pain reported by the patient immediately following 
propofol injection, with or without a vibration analgesia adjunct. Secondary outcomes will include 
subgroup analysis for responses in pain as stratified by pathology, age, sex, and ethnicity.  
Intervention  
Patients will be randomized to one of two treatment groups. Randomization will be performed by 
placing equal numbers of indicators for each treatment group in opaque, sealed envelopes, 
which will be shuffled. The surgeon will have access to a kit which contains these envelopes. 
One card will be selected in sequence from the pre-shuffled stack for each patient who gives 
consent to participate in the study.  
The intervention group will receive vibration only, with application of the BUZZY device just 
proximal to the intravenous infusion site immediately before and during propofol infusion. 
Propofol will be administered according to the institution's standard weight-based dosing (2 
mg/kg) infused over 3 minutes, repeated as needed to achieve the desired sedation level.  
Immediately following intervention, patients will be asked to rate the discomfort of the infusion 
on both a Numeric Rating Scale, with a number between 0 and 10, and a Visual Analogue 
Scale, by placing a mark on a continuous 10-cm line corresponding to their level of perceived 
pain. Additionally, two trained study investigators (one blinded to treatment group) will document 
the subject's perceived maximum pain/discomfort using a four-point pain manifestation scale as 
described in the above "Study Design" section. These values will be used to compare efficacy 
between each intervention arm as described in the Statistics section.  
With regards to safety outcomes, no significant safety issues are anticipated beyond those 
inherent to established practice.  
Response cards will not contain any identifiable patient information and will be linked to consent 
forms only through a numerical key. Consent forms will be stored separately in a secured in-
hospital location following each patient interaction.  
Intervention will be performed in the operating room during general anesthesia induction, as 
indicated, following acquisition of patient consent and randomization to a treatment arm as 
described above. Only a single intervention will be performed. Routine office follow-up will be 
offered to each patient for longitudinal management of any potential harms.  
Population  
Patients will be recruited from Montefiore Medical Center, Hutchinson ambulatory surgery 
center in the preoperative holding area prior to their surgery.  
The study sample size will need to be approximately 100 patients, 50 in each treatment arm, to 
achieve a power of 80% to detect a difference of 10 mm on the Visual Analogue Scale between 
any two study arms. This was based upon a previous study (Nakayama et al. 2001) which 
demonstrated a mean reduction in discomfort between buffered and unbuffered lidocaine of 1.0 
on the Numeric Rating Scale (from 3.5 to 2.5, with a SD of 1.4).  
Given that the study involves a single interaction, there is no dropping out from the study or 
loss-to-follow-up anticipated.  

Inclusion and exclusion criteria are described in the above sections. Specifically, however, 
minors may not be recruited into the study, as the Visual Analogue Scale is not considered 
reliable for that age group (please see Study Design section).  
The consent form will be provided in English, and will be reviewed via translation phone for non-
English-speakers, provided that the treating or examining physician is not fluent in the patient’s 
preferred language.  
No tissue specimens or blood samples will be obtained from participating patients. Recruitment  
Patients will be recruited into the study by the surgeon prior to their operation. No additional 
recruitment materials will be utilized. The study will be explained in-person and consent 
obtained with appropriate documentation. Privacy will be protected by keeping the consent 
documentation in a separate, locked, secure location from the response cards.  
Informed Consent  
The informed consent form in use for this study is based upon the Einstein IRB recommended 
template and has been included with this study application.  
Informed consent will be obtained in the preoperative holding area where the patient is spoken 
to by both the anesthesiologist and surgeon. Eligible patients will be given the opportunity to 
enroll in the study after it has been determined that they will receive propofol infusion as part of 
their general anesthesia.  
If they prefer to forgo study participation, they will receive the Standard Treatment and will not 
be enrolled; no information from the encounter, except a running count of individuals who 
refused to participate, will be recorded for use in the study. There is no requirement for a waiver 
of informed consent.  
This study will be performed without additional cost to participating patients and no 
renumeration will be offered for participation.  
All enrolling physicians will be employees of Montefiore Medical Center or the New York City 
Health and Hospitals Corporation and will have received training in accordance to the Health 
Information Portability and Accountability Act.  
Risks/Benefits  
Risks associated with the BUZZY(tm) device  
3  
There are no known risks for the use of the BUZZY(tm) device, which is registered as an FDA 
class I device ("therapeutic massager").  
Risks to privacy  

The only identifiable patient information in this study will be the consent form, which will be 
linked to the corresponding response card by a numerical key. The consent forms will be 
collected daily and placed in a separate, secure location. No component of this study will be 
videotaped for research purposes.  
Benefits  
Patients who agree to participate in this study will be given the chance to receive an analgesic 
modality (vibration) to reduce the pain of local anesthetic injection. This is expected to reduce 
the discomfort of propofol infusion.  
This study will benefit general practice by helping reduce pain with propofol infusions and 
become the new standard of care for its administration. There is a non-negligible cost 
associated with its use.  
Statistical Methods 
All data will be entered into a single SPSS database. ANOVA will be performed to  
determine if significant differences are present between study groups in terms of 
demographic/injury characteristics and the primary outcome. Univariate analysis will be 
performed on the demographic and injury characteristic to determine if any of them have a 
significant effect on the primary outcome. If any individual characteristic is found to have a 
significant effect, multiple linear regression will be performed to control for potential 
confounders. Furthermore, a correlation coefficient will be utilized to assess the inter-rater 
agreement for the visual analog scale pain scoring between the two observers.  
As no intervention in this study entails significant risk above that entailed by the standard-of-
care, there is no plan for interim analysis or early termination of the study.  
Since this investigation involves only a single patient interaction, there are no anticipated issues 
regarding loss-to-follow-up.  
Data Quality Control 
The primary data points for this study are the Visual Analogue Scale (VAS) and  
Numerical Rating Scale (NRS) of pain, as reported by patients immediately following infusion of 
propofol as well as those perceived by study investigators as detailed above. The NRS, 
although not necessarily as reliable as the VAS, is a single whole number, which cannot be 
subject to interpretation by the examiner. The VAS is measured from a value of 0-10cm along a 
continuous line, and the patient is asked to place a mark on the line at a point at which, they 
feel, corresponds to the level of their pain. This value will be measured by a third, independent 
investigator not otherwise involved in the study.  
Following acquisition of the NRS and VAS pain values, these values will be entered in the study 
database, which will be maintained solely by the primary investigators, keyed to individual 
participants' consent forms by a non-identifying serial number. Again, the consent forms will be 
stored in a separate location. Given the single site and relatively small size of study subjects, 
close monitoring by the study investigator is an adequate level of monitoring for this advice, as 
outlined and described in the DSM policy. 31 March 2018  

All statistical analyses will be reviewed and verified with a faculty statistician.  
Results 
A total of 100 participants were recruited between April 2019 and November 2019, 50 in 
each study arm (control versus treatment group) with no losses or exclusions after 
randomization; recruitment was stopped once the calculated sample size was obtained. The 
control group and treatment group were comparable with respect to demographic 
characteristics. The mean age of patients was 50.8 ± 13.9 years. 39% of patients were males. 
The mean patient BMI was 28.5. Agreement between the attending anesthesiologist and CRNA 
observers regarding pain scores (scale from 0 to 3 points) was excellent and statistically 
significant, with weight kappa (κw) = 0.82 (p<0.001).   
A significantly lower incidence of pain was found in the treatment group as compared to 
the control group. Nine (18.0%) patients in the treatment group had pain during propofol 
injection as compared to nineteen (38.0%) patients in the control group (p=0.03), yielding a risk 
difference of 20.0%. Significantly lower severity of pain was found in the treatment group as 
compared to the control group. The median summative pain score (scale: 1-6) in the treatment 
group was 1 [IQR: 1-2] as compared to 2 [IQR: 2-4] in the control group (p <0.01). 
A higher incidence of pain with propofol infusion was noted in patients with an 
intravenous catheter location in the hand as compared to other locations with a risk ratio of 2.7 
(95% CI:1.07-6.97, p=0.04). A log-binomial regression analysis was performed adjusting for the 
intravenous catheter location. A significantly lower incidence of pain in the treatment group 
versus the control group was maintained in the regression analysis with a risk ratio of 0.44 (95% 
CI:0.22-0.86, p=0.02).  
The propofol dose did not differ significantly between the treatment and control groups 
and did not differ significantly in patients with or without pain (p=0.95 and p=0.30, respectively). 
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