Clinical trial NCT02229578
Conditions: Pain
Keywords: Burn pain lidocaine donor site pain Narcotic use
Sponsor: University of Florida
Start date: 2014-09-01; Completion date: 2017-11-14
Enrollment: 34 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Burn pain is known to be one the most severe forms of acute pain often requiring large amounts of narcotics in addition to other adjuvants. Topical lidocaine is effective for controlling pain in various settings including dressing changes of burns. The aim of this study is to demonstrate the effectiveness of topical lidocaine in decreasing pain scores and narcotic requirements when applied to donor graft sites while at the same time not interfering with the standard of care TheraBond dressing. During this study the investiagtors will be monitoring for evidence of delayed wound healing, and surgical site infection.

Detailed description:
Pain from burns is a severe form of acute pain that requires aggressive use of opioids. Even with the implementation of multiple modalities for analgesia, pain from skin debridements and grafting procedures remains a challenge to control. Local anesthetics have been used for pain relief in burn patients previously as a topical gel or IV infusion and have been found to significantly reduce medication consumption, without apparent adverse effects on wound healing. Lidocaine actually has potent anti-inflammatory effects which could be advantageous on wounds. In addition, topical application of lidocaine to wounds result in different degrees of systemic absorption. High concentrations of lidocaine have potential for central nervous system (seizures (\>5mg/L)) and cardiovascular toxicity (arrhythmias (\>9mg/L)). Plasma concentration of lidocaine depend upon drug dose, rate of absorption, patient weight, physical status and thickness of skin harvested. A prior study where up to 6.7mg/kg of 2% lidocaine with epinephrine was sprayed on donor graft sites found that systemic lidocaine levels were far below toxic levels at their peak (average level of 1.4, with maximum level at 2.2). In this study the levels peaked between 30 and 60 minutes and systemic levels of lidocaine were detectable 6 hours following application of the solution. Studies have demonstrated the beneficial effects of systemic lidocaine administered via IV infusions in reducing perioperative pain scores.Topical lidocaine is effective as a topical anesthetic in multiple clinical trials however only two studies to date has shown that topical lidocaine applied to skin-harvest sites produces an analgesic effect, reduces narcotic requirements while not affecting wound healing or causing toxic blood concentrations. In both these studies systemic intravenous lidocaine levels were monitored and were found to be significantly below toxic limits. The use of topical lidocaine on donor sites is still not widely used, partly for fear the lidocaine will interfere with wound healing and/or dressing adherence. No study to date has demonstrated lidocaine solution to be effective on burn sites when used in conjunction with TheraBond silver foam dressing. TheraBond is an absorbent, atraumatic dressing coated with ionic silver that is routinely used on donor sites at the University of Florida. This study will also offer additional supporting evidence that topical lidocaine is effective in post operative pain management of donor skin sites and should be more widely utilized. In addition, this study will serve as a stepping stone for analyzing different local anesthetic solutions in the future and the potential for reapplication to surgical sites.

The purpose of this study is to offer the medical community data on a simple and relatively cheap adjuvant that can be utilized to help reduce the amount of post-operative pain and narcotic requirement in burn patients requiring skin grafts.

Arms: arm 1: Subjects in this group will receive a nonpyrogenic solution of lidocaine 2% in isotonic saline (Solution A) sprayed on the donor site of the grafted skin prior to emergence from general anesthesia. A total maximum of 7mg/kg of lidocaine solution will be available for administration. Prior to spraying of the Solution A, the donor site will be soaked with epinephrine soaked towels as per routine burn care. The site will then be covered with TheraBond dressing as per standard burn care. arm 2: Subjects in this group will receive a nonpyrogenic solution of isotonic saline (Solution B) sprayed over the donor site. Prior to spraying of the Solution B, the donor site will be soaked with epinephrine soaked towels as per routine burn care. The site will then be covered with TheraBond dressing as per standard burn care.
Interventions: intervention 1: Lidocaine intervention 2: Placebo
Intervention descriptions: intervention 1: Subjects in this group will receive a nonpyrogenic solution of lidocaine 2% in isotonic saline (Solution A) sprayed on the donor site of the grafted skin prior to emergence from general anesthesia. A total maximum of 7mg/kg of lidocaine solution will be available for administration. Prior to spraying of the Solution A, the donor site will be soaked with epinephrine soaked towels as per routine burn care. The site will then be covered with TheraBond dressing as per standard burn care. intervention 2: Subjects in this group will receive a nonpyrogenic solution of isotonic saline (Solution B) sprayed over the donor site. Prior to spraying of the Solution B, the donor site will be soaked with epinephrine soaked towels as per routine burn care. The site will then be covered with TheraBond dressing as per standard burn care.

Protocol documents:
Prot_SAP_000.pdf: 
 
 
 
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Project Title: 
LIDOCAINE IN THE TREATMENT OF POST-OPERATIVE PAIN 
MANAGEMENTFROM A DONOR SITE AFTER SPLIT THICKNES SKIN GRAFT 
HARVESTING FOLLOWING BURN INJURY OR WOUND TREATMENTS 
 
 
NCT #: 
NCT02229578 
 
Document date: 
December 08, 2016 
 
 


 
 
 
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Protocol 
1. Project Title: 
 
 
LIDOCAINE IN THE TREATMENT OF POST-OPERATIVE PAIN 
MANAGEMENTFROM A DONOR SITE AFTER SPLIT THICKNES SKIN GRAFT 
HARVESTING FOLLOWING BURN INJURY OR WOUND TREATMENTS 
2. Investigator(s):  
Brenda Fahy, MD  
 
 
 
 
 
James Gallagher, MD 
 
 
 
 
 
Adrian Ching, MD 
 
 
 
 
 
Gena Roberts, ARNP 
 
 
 
 
 
Terrie Vasilopoulos 
3. Abstract: 
Burn pain is known to be one the most severe forms of acute pain often requiring 
large amounts of narcotics in addition to other adjuvants.  Wounds can also cause a 
great deal of pain in this population.  Topical lidocaine is effective for controlling pain 
in various settings including dressing changes of burns.  The aim of this study is to 
demonstrate the effectiveness of topical lidocaine in decreasing pain scores and 
narcotic requirements when applied to donor graft sites while at the same time not 
interfering with the standard of care TheraBond dressing.  During this study we will be 
monitoring for evidence of delayed wound healing, and surgical site infection. 
4.  Background: 
Pain from burns is a severe form of acute pain that requires aggressive use of 
opiods.1 Even with the implementation of multiple modalities for analgesia, pain from 
skin debridements and grafting procedures remains a challenge to control.2,3 Local 
anesthetics have been used for pain relief in burn patients previously as a topical gel 
or IV infusion and have been found to significantly reduce medication consumption, 
without apparent adverse effects on wound healing. 2,4,5 Lidocaine actually has 
potent anti-inflammatory effects which could be advantageous on wounds.1 In 
addition, topical application of lidocaine to wounds result in different degrees of 
systemic absorption. High concentrations of lidocaine have potential for central 
nervous system (seizures (>5mg/L)) and cardiovascular toxicity (arrhythmias 
(>9mg/L)).4 Plasma concentration of lidocaine depend upon drug dose, rate of 
absorption, patient weight, physical status and thickness of skin harvested.6A prior 
study where up to 6.7mg/kg of 2% lidocaine with epinephrine was sprayed on donor 


 
 
 
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graft sites found that systemic lidocaine levels were far below toxic levels at their 
peak (average level of 1.4, with maximum level at 2.2). In this study the levels 
peaked between 30 and 60 minutes and systemic levels of lidocaine were detectable 
6 hours following application of the solution.2Studies have demonstrated the 
beneficial effects of systemic lidocaine administered via IV infusions in reducing 
perioperative pain scores.7, 8Topical lidocaine is effective as a topical anesthetic in 
multiple clinical trials however only two studies to date has shown that topical 
lidocaine applied to skin-harvest sites produces an analgesic effect, reduces narcotic 
requirements while not affecting wound healing or causing toxic blood 
concentrations. In both these studies systemic intravenous lidocaine levels were 
monitored and were found to be significantly below toxic limits.2,9  The use of topical 
lidocaine on donor sites is still not widely used, partly for fear the lidocaine will 
interfere with wound healing and/or dressing adherence. No study to date has 
demonstrated lidocaine solution to be effective on burn sites when used in 
conjunction with TheraBond silver foam dressing. TheraBond is an absorbent, 
atraumatic dressing coated with ionic silver that is routinely used on donor sites at 
our institution. This study will also offer additional supporting evidence that topical 
lidocaine is effective in post-operative pain management of donor skin sites and 
should be more widely utilized. In addition, this study will serve as a stepping stone 
for analyzing different local anesthetic solutions in the future and the potential for 
reapplication to surgical sites.   
5. Specific Aims: 
The purpose of this study is to offer the medical community data on a simple and 
relatively cheap adjuvant that can be utilized to help reduce the amount of post-
operative pain and narcotic requirement in burn and wound patients requiring skin 
grafts. 
 
6. Research Plan: 
 
Study Design 
 
a) Randomized Controlled Double-Blind Study 
b) Burn and wound patients undergoing general anesthesia for split thickness 
skin graft with a 1-15% TBSA donor site who will be treated at UF Health 
Shands Hospital  
c) Consent will be obtained from non-intubated patients willing to participate in 
the study that are admitted to the Burn Service for treatment of their burn or 
wound. All patients will undergo general anesthesia. Standard induction will 
be performed with Fentanyl and Propofol. Maintenance will primarily be with 
the volatile agent sevofluorane. Acetaminophen 1g IV and Ketorolac 30mg IV 
will be administered for baseline pain control intraoperative within the last 30 
minutes prior to extubation. Fentanyl, Hydromorphone or Morphine will be 


 
 
 
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titrated in at end of the case as part of standard management. 
Hydromorphone, as needed (PRN), orders will be written for pain control in 
the recovery room as well as one time dose of Oxycodone 5-15mg PO. If 
patient requires more than 2mg of Hydromorphone then subsequent pain will 
be treated with Ketamine IV (10mg every 15 minutes up to 50mg total) and 1-
2mg of IV midazolam. If pain is still not adequately controlled patient will be 
treated with an additional 2mg of Hydromorphone IV and Hydromorphone 
PCA will be initiated. Once discharged from the PACU to the surgical floor the 
patient will have PRN Oxycodone PO every 4 hours and/or Hydromorphone 
PO every 4 hours in addition to PRN Hydromorphone 0.2-0.5mg available. If 
pain control is still not adequate patient will be started on Hydromorphone 
PCA. The amount of hydromorphone required in PACU and in the first 24 
hours following surgery will be compared between the two groups as well as 
self-reported donor site and overall pain according to the Verbal Numerical 
Rating Scale (VNRS) obtained from the patient by Research staff and by the 
hospital staff per standard of care. 
d) Lidocaine 2% with Epinephrine 10µg/mL will be placed on the donor site 
immediately following harvesting until hemostasis has been obtained per the 
surgeon. The total of up to 7mg/kg, as recommended by leading anesthesia 
textbooks, of lidocaine solution will also be sprayed onto the patient’s donor 
site based on patient’s ideal weight (BMI 25 or actual patient’s weight if BMI 
<25).10 
e) 50patients split into two(study & control) groups.  
a. Group A patients will  have sterile 2% lidocaine with Epinephrine 10 
µg/mL (Solution A1) soaked in surgical grade cotton applied to the 
donor site immediately after donor harvest until hemostasis is obtained 
according to the surgeon. If additional hemostasis is deemed 
necessary by the surgeon following use of 20cc (1 vial) of this Solution 
A1 then additional Epinephrine 10µg/mL will be used as per standard 
burn protocol. Following hemostasis, patients will have a sterile, 
nonpyrogenic solution of lidocaine 2% in isotonic saline (Solution A2) 
sprayed on the donor site of the grafted skin prior to emergence from 
general anesthesia. A maximum of 7mg/kg of lidocaine solution will be 
available for spraying. The site will then be covered with TheraBond 
dressing as per standard burn care used at our institution.  
b. Group B (control group) patients will have sterile Epinephrine 10µg/mL 
solution (Solution B1) soaked in surgical grade cotton applied to the 
donor site immediately after donor harvest. A 20cc aliquot will prepared 
in such a way as to be indistinguishable from Solution A1 by the OR 
team. If additional hemostasis is deemed necessary by the surgeon 
following use of 20cc (1 vial) of this Solution B1 then additional 
Epinephrine 10µg/mL will be used as per standard burn protocol.  
Following hemostasis, patients will have a control (placebo) sterile, 
nonpyrogenic solution of isotonic saline (Solution B2) sprayed over the 
donor site.  The site will then be covered with TheraBond dressing as 
per standard burn care used at our institution.  


 
 
 
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f) Assessment of the donor sites using the VNRS pain scores will be compared 
between groups in addition to the amount of narcotic pain medication required 
by these two groups. The amount of narcotic utilized will be analyzed per 
ideal body weight, per actual body weight in addition to donor site area.  
g) Lidocaine levels will be drawn at sixty minutes and six hours from application 
of study solution. These levels will be analyzed on a per patient and per graft 
size area basis to trend for systemic levels.  
h) Any adverse event occurring with the patient will be analyzed on a case-by-
case basis. Wound infection rates of the donor sites at post op day 14-21 +/-5 
days will be compared between the two groups. Any adverse event deemed 
serious by the Principal Investigator will be submitted to the Institutional 
Review Board per institution policy. 
i) All care offered during this treatment, including intraoperative medication use, 
surgical application of dressing and post-operative wound assessments are 
currently part of standard burn care at our institution. The only new variable 
we are analyzing is the addition of the lidocaine/placebo solution to the donor 
site intraoperatively.  
 
Intraoperatively a TheraBond dressing will be applied to the donor site that later 
“falls off” once the site has healed.  Outer dressings of gauze, Bioguard and 
Acewraps will also be applied, covering the Therabond and will be changed daily 
per standard of care. Wound healing of the donor site will be evaluated visually 
by the burn research team and the time in days of TheraBond dressing removal 
will be analyzed. In addition, photographs of the donor sites will be obtained 
intraoperatively and at the time the TheraBond comes off.  
Study Procedures 
 
a. Subject selection procedures 
i. Inclusion criteria: Adult patients who have suffered second to 
third degree burns or have a wound requiring a single split 
thickness skin graft surgery. Donor sites will be estimated to be 
between 1-15% TBSA. Patients who have history of major renal 
and/or liver dysfunction, history of seizures or major neurologic 
deficiencies, allergy to local anesthetics, reported allergy to 
hydromorphone, pregnancy, or currently have other injuries that 
significantly contribute to pain (i.e. multi-trauma patients) will be 
excluded from the study.  
ii. Consent will be obtained from all patients. The risk and benefit 
topical lidocaine will be explained to each patient and a consent 
for this study will be obtained.Burn and wound patients require 
high doses during wound related procedures and for post-
operative pain control. At other times their background pain is 
easily controlled by much lower doses of narcotics; they remain 
alert and are capable of making complex decisions.  


 
 
 
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iii. If a patient is found to be in pain out of proportion to injury at 
hand and demonstrate an inability to focus on the consent they 
will not be considered for enrollment in the study.  
b. Randomization procedures: Numerical randomization will be created 
using a computer generated numbers.  Randomization envelopes will 
be created by research staff and maintained by the Investigational 
Drug Pharmacy.  The Burn Study Team will alert the Investigational 
Drug Pharmacy to randomize each patient.    The Investigational Drug 
Pharmacy will dispense the appropriate blinded solution for treatment. 
The Investigational Drug Pharmacy will dispense Lidocaine with 
Epinephrine or Epinephrine alone in blinded fashion for the donor site 
soaks. A 20cc bottle of Lidocaine with Epinephrine or Epinephrine 
alone will be emptied into a sterile unlabeled container prior to 
application of sprayed study treatment. The surgeon and OR team will 
remain blinded for this portion of the study. If additional hemostasis is 
required beyond the first study soak treatment; then the standard of 
care epinephrine soak will be utilized. The Investigational Drug 
Pharmacy will also dispense the randomized spray study treatment in 
an assembled applicator (LMA MADgic™)purchased for this project 
only.  No unblinding identifiers will be on either applicators. The 
investigator will be blinded to all groups. Study Intervention: 
i. Group A (Lidocaine Treatment Group): Graft site hemostasis will 
be obtained with 2% lidocaine and epinephrine 10µg/mL 
solution in normal saline soaked in surgical grade cotton gauze 
and placed over donor site for time determined by surgeon. 
Following hemostasis, 7mg/kg of 2% Lidocaine solution will then 
be sprayed on patient’s donor site while under general 
anesthesia by burn surgeon in a sterile fashion Upon 
emergence and transfer to PACU patient will be asked to rate 
his/her pain according to the VNRS for both donor site and 
overall pain. The amount of narcotics required in PACU and first 
24 hours on floor will be documented. Rate of increase of 
narcotic requirement within the first 24 hours will also be 
analyzed. VNRS scores will be obtained immediately post 
operatively on arrival to PACU and in 24 hours.  
ii. Group B(Placebo Group): Graft site hemostasis will be obtained 
with a epinephrine 10µg/mL solution in normal saline soaked in 
surgical grade cotton gauze and placed over donor site for time 
determined by surgeon. Following hemostasisa control solution 
will be sprayed on patient’s donor site while under general 
anesthesia by burn surgeon in a sterile fashion. Upon 
emergence and transfer to PACU patient will be asked to rate 
his/her pain according to the VNRS for both donor site and 
overall pain. The amount of narcotics required in PACU and first 
24 hours on floor will be documented. Rate of increase of 
narcotic requirement within the first 24 hours will also be 


 
 
 
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analyzed. VNRS scores will be obtained immediately post 
operatively on arrival to PACU, 6 hours post treatment during 
blood draw and in 24 hours for both donor site and overall pain.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study Table of Events 
 
Study 
Assessments 
Baseline 
Surgical 
Procedure 
0-24 hours 
post op 
24-48 hours 
post op 
Follow up 
(14-21 
days)* 
 
Informed Consent 
 
X 
 
 
 
 
 
Inclusion/Exclusion 
 
X 
 
 
 
 
 
Demographic Data 
 
X 
 
 
 
 
 
Medical History 
 
X 
 
 
 
 
 
Physical Exam 
 
X 
 
 
 
 
 
Randomization 
 
 
X 
 
 
 
 
Treatment 
 
 
X 
 
 
 
OR Data 
Collection 
 
 
X 
 
 
 
VNRS Pain 
Assessment 
 
 
 
X** 
 
X** 
 
Self-Reported Pain 
Assessment 
 
 
 
X 
 
X 
 
Wound Healing 
Assessment 
 
 
 
 
 
X 
 
Photographs 
 
 
X 
 
 
 
X 


 
 
 
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Narcotic 
Medication Data 
Collection 
 
 
 
X 
 
 
X 
 
 
X 
 
Adverse/SAE 
Assessment 
 
X 
 
X 
 
X 
 
X 
 
X 
Lidocaine Level  
 
 
 
X*** 
 
 
* (+/- 5 days) 
**Performed at 30 minutes after extubation, 2 hours, 6 hours and 24 hours post-opfor both donor site and overall pain 
***Performed at 60(+/-30 minutes) minutes and 6 hours (+/-60 minutes) post op 
 
 
Safety Monitoring Plan 
 
a. The likelihood of adverse events in this study is very small. Lidocaine 
spray doses will be calculated (7mg/kg based on ideal body weight) to 
ensure patient is receiving safe doses. A safety analysis performed on our 
first 15 patients proved safety. All lidocaine levels obtained demonstrated 
levels significantly lower than potentially toxic dosing. We believe there 
could be improved pain control if more appropriate (higher) lidocaine 
doses are utilized. The method suggested for hemostasis with lidocaine 
and epinephrine is standard of care at some institutions including our own. 
It is regularly used by the ENT service. In addition, one of the surgeons in 
our study has used this method in the past. 
b. Patients will be monitored with pulse oximetry overnight per standard of 
care.  
c. All patients enrolled in the study will have risks and benefits thoroughly 
explained to them.  
d. Any adverse events will be well documented and thoroughly investigated. 
Seriousness of event will be assessed by the Principal Investigator.  All 
events deemed serious will be submitted to the University of Florida 
Institutional Review Board in accordance with institutional policy. 
e. Dressing site will be evaluated daily per standard of care by the burn team 
until hospital discharge.  
f. After 10 additional evaluable patients, have been enrolled a secondsafety 
analysis will be performed; all investigators will be involved in data 
interpretation.  
 
Analysis Plan 
 
An independent groups t-test (Student’s t-test) will be performed to 
compare the mean rating between the difference of the two reported pain 
scale ratings. Each patient will be used as his/her own control by 
comparing the amount of narcotics utilized prior to surgery. An alpha level 
of 0.05 and power of 0.8 will be used to address the difference in the two 
groups. Given the desired alpha the sample size was estimated by pre-
determined tables for certain values, by Mead’s resource equation. With 
an effect size (Cohen’s d) of 0.8 it is estimated that 25patients in each 


 
 
 
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group will be needed in order to show statistical significance. An interim 
analysis will be conducted at 10 patients in each group and significance 
will be analyzed.  
 
The amount of hydromorphone utilized in the PACU immediately post op 
and within the first 24 hours will be compared between the two groups and 
trended within the same group. Once again, an independent groups t-test 
will be performed to compare the mean quantity of hydromorphone 
required between the two groups. An alpha level of 0.05 and power of 0.8 
will be used to address the difference in the two groups.  
 
 
 
7.  Possible Discomforts and Risks: 
 
The patient’s regular medical care will not change because they are enrolled in this 
study. 
Possible risks to you may include:  
• The risks from skin grafting and donor site include those associated with any 
surgical procedure that involves general anesthesia.  These include reactions 
to the anesthesia, medications, nausea, pain, problems breathing, excessive 
bleeding, and infection.   
• If a wound becomes infected, it may result in the need for further surgical 
treatment.  Surgical treatment could include debridement of the wounded 
area (surgical removal of dead or infected tissue of the wound), and/or 
regrafting. Because your doctor looks at the wounds very closely, he/she will 
try to take care of any complications as fast as they can.  The treatment of 
side effects and complications will be the same that would be expected for the 
treatment of side effects and complications for any skin grafting and donor 
site procedure performed at the hospital. 
• Side effects of Lidocaine include: Nausea, drowsiness, mental/mood 
changes, ringing in the ears, dizziness, vision changes, tremors, numbness, 
headache and backache.  Serious adverse effects could include fever, 
unusually fast and slow pulse, trouble breathing, seizures and chest pain.  An 
allergic reaction to Lidocaine could include: rash, itching, swelling, dizziness, 
and trouble breathing. 
• Side effects of drawing blood from a vein include discomfort at the site of 
puncture; possible bruising and swelling around the puncture site; rarely an 
infection; and, uncommonly, faintness from the procedure.  Blood drawn each 
time will be approximately 5 teaspoons.  The total amount drawn during the 
study will be approximately 10 teaspoons. 


 
 
 
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8. Possible Benefits: 
Patients randomized to the treatment group may have increased satisfaction, 
increased pain control, decreased narcotic usage, and a decrease in chronic pain. 
9. Conflict of Interest: 
There is no conflict of interest involved with this study beyond professional benefit 
from academic publication or presentation of results. 
 
 


 
 
 
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Literature Cited 
 
1. Pal SK, Cortiella J, Herndon D. Adjunctive methods of pain control in 
burns. Burns 1997;23:404–12.  
2. Jellish WS, Gamelli RL, Furry PA, McGill VL, Fluder EM. Effect of topical 
local anesthetic application to skin harvest sites for pain management in 
burn patients undergoing skin-grafting procedures. Ann Surg 
1999;229:115–120. 
3. Buvanendran A, Kroin JS. Multimodal analgesia for controlling acute 
postoperative pain. Curr Opin Anaesthesiol 2009;22:588–93. 
4. Patterson DR, Hoflund H, Espey K, Sharar S. Pain management. Burns 
2004;30:A5–10. 
5. Bulmer JN, Duckett AC. Absorption of lignocaine through split-skin donor 
sites. Anaesthesia 1985;40:808–9. 
6. Derek JD. Local and regional anaesthesia. Baillieres Clin Anaesthesiol 
1987;1:715–28. 
7. Oliverira G S., et al. Systemic Lidocaine to Improve Postoperative Quality 
of Recovery After Ambulatory Laparoscopic Surgery. Anesth Analg 
Volume X, Number X, 2012.  
8. Cassuto, J., et all. Inhibition of Postoperative Pain by Continuous Low-
Dose Intravenous Infusion of Lidocaine. Anesth Analg 1985;64;971-4 
9. Desai C. et. Al. Effectiveness of a topical local anaesthetic spray as 
analgesia for dressing changes: A double-blinded randomized pilot trial 
comparing an emulsion with an aqueous lidocaine formulation. JBUR-
4055; No. of Pages 7 
10. Frank SG, Lalonde DH. How acidic is the lidocaine we are injection, and 
how much bicarbonate should we add? Can J Plast Surg. 2012 Summer; 
20(2)71-3 
11. Hobeich, P. et al. A Prospective, Randomized Double-blind Comparison of 
the Injection Pain and Anesthetic Onset of 2% Lidocaine with 1:100,000 
Epinephrine Buffered with 5% and 10% Sodium Bicarbonate in Maxillary 
Infiltrations. JOE V39, N5, May 2013.  
12. Miller R. Anaesthesia, 5th edn. Philadelphia: Churchill Livingstone, 2000. 
 
 


 
 
 
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Appendix A. 
DATA COLLECTION  POINTS 
Age 
Race 
Sex 
Height 
Weight  
BMI 
Date of Injury/Wound 
Mechanism of Injury/Wound 
TBSA % Burned /Size of wound 
Medical History 
Physical Exam 
Randomization 
OR Procedure 
OR Date 
OR Incision Time 
OR ExtubationTime 
OR Medication Data Collection 
Donor Site Dimensions 
Lidocaine levels at 60 minutes and 6 hours post op 
Time of Study Treatment Soak Placement 
Additional Epinephrine Soak Required 
Time of Study Treatment Spray Placement 
Time of Therabond Placement 


 
 
 
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Time of PACU/BICU Admission (Post-operatively) 
PACU/BICU Post –op Narcotic Medication 
Documentation of Verbal Numerical Rating Scale Pain Assessment (Time): 30 
minutes after extubation, 2 hours, 6 hours and 24 hours post op obtained by research 
staff for both donor site and overall pain 
Self- Reported Pain Assessment (Time): Collect from EPIC for first 24 hours  
Wound Healing Assessment (14-21 days post op[+/-5days]) Performed per standard 
of care 
Photographs (OR and 14-21 days post op[+/-5days]) 
Adverse/SA Event Assessment 
Overall Narcotic Medication Data Collection from EPIC (0-72 hours post op) 
Date of new onset infection of donor site 
Antibiotics for donor site infection 
 
 
 
 
 
 
 
 
 
 
APPENDIX B. 
 
Verbal Numeric Pain Rating Scale 


 
 
 
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Appendix C. 
 
 
Case Report Forms 
 


 
 
 
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Patient Initials:  __ __ __  
 
 
 
 
Page 1 of 1
 
Patient ID:   _________  
 
 
 
 
___-___-___ 
 
 
 
 
 
 
 
 
 
Date 
 
Inclusion/Exclusion Criteria 
 
Inclusion Criteria (all must be checked Y) 
 
 
 
 Y 
 N 
 
[  ] 
[  ]  
 
Is the subject 18 years of age or older? 
[  ] 
[  ] 
 
Has the subject suffered second to third degree burns or a wound  
 
 
 
requiring a single splitthickness skin graft surgery? 
[  ] 
[  ] 
 
Are donor sites to be harvested estimated to be between 1-15%TBSA? 
[  ] 
[  ] 
 
Is the subject willing and able to give informed consent?   
ICF Date: _____-____-____ 
[  ]    
[  ] 
 
The subject is not participating in another interventional clinical trial? 
 
Exclusion Criteria (all must be checked N) 


 
 
 
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 Y 
 N 
N/A 
[  ]    
[  ] 
[  ] 
Is the subject pregnant? 
Pregnancy Test Type: ________ Pregnancy Test Date: ____-____-____ 
[  ] 
[  ] 
 
Does the subject have a history of major renal or liver dysfunction?  
[  ] 
[  ] 
 
Does the subject have a history of seizures or major neurologic deficiencies? 
[  ] 
[  ] 
 
Does the subject have allergies to local anesthetics or hydromorphone?        [  
] 
[  ] 
 
Does the subject have any other injuries that could significantly contribute to                        
 
 
 
pain? (ex: multi-trauma patient) 
 
 
 
 
 
 
Eligibility Exceptions: 
________________________________________________________________
________________________________________________________________
________________________________________________________________
________________________________________________________________
________________________________________________________________
________________________________________________________________
________________________________________________________________ 
 
Patient Initials:  __ __ __  
 
 
 
 
Page 1 of 2
 
Patient ID:   ___-____  
 
 
 
 
___-___-___ 
 
 
 
 
 
 
 
 
 
Date
Baseline 
 
Demographics: 
 
Date of Burn Injury: ____ / ____ / ____                                Date of Admission:____ / ____ / ____ 
 
 
Age:  ____                                   Sex: [ ] M  [  ] F              Race:  
[ ] Caucasian 
 
 
 
 
 
 
 
 
 
[ ] African American 
 
 
 
 
 
 
 
 
 
[ ] Asian 
Height: _____ in.Weight: ______kgs.BMI: ______ 
[ ] Hispanic 
 
 
 
 
 
 
 
 
 
[ ] Other: ______________ 
Mechanism of Injury: 
 
 
 
 
[  ] Flame 
 
[  ] Scald 
 
[  ] Chemical 
 
 
 
[  ] Electrical 
 
[  ] Contact 
 
[  ] Other (Non-Burn) 
 
 
 
 
TBSA % Total:   
 
____%  
or [  ] not applicable 
 
TBSA % Partial Thickness:  
____%  
or   [  ] not applicable 
 


 
 
 
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TBSA % Full Thickness:     
____%  
or   [  ] not applicable 
 
 
 
Illnesses/Past Medical History: 
 
 
 
[  ] None 
 
[  ] Cancer 
 
[  ] COPD 
 
 
 
[  ] CV Disease  
[  ] Diabetes 
 
[  ] ETOH  
 
 
 
[  ] Hypertension 
[  ] Renal Disease 
[  ] Substance Abuse 
 
 
 
[  ] Seizure Disorder 
[  ] Stroke 
 
[  ] Other: Specify ______________ 
 
 
Comments: 
________________________________________________________________
________________________________________________________________
________________________________________________________________
________________________________________________________________
________________________________________________________________ 
 
Patient Initials:  __ __ __  
 
 
 
 
Page 2 of 2
 
Patient ID:   ___-____  
 
 
 
 
___-___-___
 
 
 
 
 
 
 
 
 
Date 
Baseline 
 
Physical Exam: 
 
Vitals:         
 
Temp: _____ C°     HR: _____ bpm   SAT: _____%    BP:  ____ /____    Resp: ____ 
 
Date of Exam: ___ / ___ /____                                     Time of Exam: ____ : ____     
 
System 
 
Abnormal 
 
Normal 
 
Explanation 
 
General 
 
 
 
 
HEENT 
 
 
 
 
Cardiovascular 
 
 
 
 
Respiratory 
 
 
 
 
Gastrointestinal 
 
 
 
 
Genitourinary 
 
 
 
 
Musculoskeletal 
 
 
 


 
 
 
Protocol #201400019 
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Skin 
 
 
 
 
Neurologic 
 
 
 
 
Psychiatric 
 
 
 
 
Endocrine 
 
 
 
 
Heme/Lymphatic 
 
 
 
 
Allergic/Immunologic 
 
 
 
 
 
 
 
 
Patient Initials:  __ __ __  
 
 
 
 
Page 1 of 1
 
Patient ID:   ___-____  
 
 
 
 
___-___-___
 
 
 
 
 
 
 
 
 
Date 
Randomization 
 
 
Date Randomized:  ___-___-___  
 
Time Randomized*:  ___: ___ 
 
 
Order placed in EPIC to Randomize/Dispense Study Medication:  
 
Date:  ____ / ____ / ____ 
 
Time: __________ 
 
 
Randomization Materials to be stored in Investigational Drug Pharmacy until study 
completion. 
 
*Time dispensed on study drug/placebo packaging 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
 
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Comments: 
________________________________________________________________
________________________________________________________________
________________________________________________________________
________________________________________________________________
________________________________________________________________
________________________________________________________________
________________________________________________________________ 
 
Patient Initials:  __ __ __  
 
 
 
 
Page 1 of 1
 
Patient ID:   ___-____  
 
 
 
 
___-___-___
 
 
 
 
 
 
 
 
 
Date 
Surgical Procedure 
 
Surgical Procedure Information: 
 
OR Date:  ____ / ____ / ____  Incision Time: ____ : ____    ExtubationTime: ____ : 
____  
 
Procedure Performed: 
 
 
 
 
Area of Donor Site Harvest*:  
[ ] Left Thigh  
 
 
 
 
 
 
[ ] Right Thigh 
 
 
 
 
 
[ ] Other: ___________ 
 
Donor Site Harvest Time: 
 
___________________ 
 
 
Donor Site Dimensions:  
 
_____ cm x _____ cm= ______ cm² 
 
Photos of Donor Sites Complete:       [ ] Yes  
[ ] No     
 
Time of Study Treatment Soaks: 
 
 
Time ON ____ : ____    
Time OFF ____ : ____     
 
Time ON ____ : ____    
Time OFF ____ : ____     
Need for additional Epinephrine Soaks: 
 
[ ] Yes  
[ ] No     
 
Time ON ____ : ____   
Time OFF ____ : ____     
 
 


 
 
 
Protocol #201400019 
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Time of Study Spray Treatment: 
           ____ : ____    
 
Time of TheraBond Placement: 
____ : ____     
 
Post Op Admit to: 
 
 
[ ] BICU    
[ ] PACU 
 
Post Op Admit Time:  
          ____ : ____     
* One page to be completed per donor site 
 
 
Patient Initials:  __ __ __  
 
 
 
 
Page 1 of 4
 
Patient ID:   ___-____  
 
 
 
 
___-___-___
 
 
 
 
 
 
 
 
 
Date 
Post-OP Study Assessments- 30 Minutes Post Extubation 
 
 
30 Minute Post-extubation VNRS Pain Assessment: 
 
Is the subject able to provide VNRS Pain Assessment related to donor site pain only: 
 
 
[ ] Yes  
[ ] No     
 
Time:  ____: ____        Score : ______ 
 
Is the subject able to provide VNRS Pain Assessment related to overall pain: 
 
 
[ ] Yes  
[ ] No     
 
Time:  ____: ____        Score : ______ 
 
 
VNRS Pain Assessment recorded by: _______________________________________ 
 
Comment:    [ ] Yes  
[ ] No     
 
 
Post-OP Study Assessments- 60 Minutes (+/- 30 minutes) 
 
 
60 Minute Post-op Lidocaine Level: 
 
Lidocaine Level Drawn By:         [ ] Shands Lab Phlebotomy      [ ] Research Staff 
 
Time of Lab Draw: 
___:___    Result: ______ mcg/mL   Normal Range 1.5-5.0 
mcg/mL 
 
Lidocaine Level added to Participant Tracking Log:   
[ ] Yes  
[ ] No     


 
 
 
Protocol #201400019 
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Comment:    [ ] Yes  
[ ] No     
 
 
 
 
 
 
 
Patient Initials:  __ __ __  
 
 
 
 
Page 2 of 4
 
Patient ID:   ___-____  
 
 
 
 
___-___-___
 
 
 
 
 
 
 
 
 
Date 
Post-OP Study Assessments- 2 Hours 
 
2 Hour  Post-op VNRS Pain Assessment: 
 
Is the subject able to provide VNRS Pain Assessment related to donor site pain only: 
 
 
[ ] Yes  
[ ] No     
 
Time:  ____: ____        Score : ______ 
 
Is the subject able to provide VNRS Pain Assessment related to overall pain: 
 
 
[ ] Yes  
[ ] No     
 
Time:  ____: ____        Score : ______ 
 
 
VNRS Pain Assessment recorded by: _______________________________________ 
 
Comment:    [ ] Yes  
[ ] No     
 
 
Post-OP Study Assessments- 6-Hours (+/-60 minutes) 
 
 
6 Hour Post-op Lidocaine Level: 
 
Lidocaine Level Drawn By:         [ ] Shands Lab Phlebotomy      [ ] Research Staff 
 
Time of Lab Draw: 
___:___    Result: ______ mcg/mL   Normal Range 1.5-5.0 
mcg/mL 
 
Lidocaine Level added to Participant Tracking Log:   
[ ] Yes  
[ ] No     
 
Comment:    [ ] Yes  
[ ] No     


 
 
 
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Patient Initials:  __ __ __  
 
 
 
 
Page 3 of 4
 
Patient ID:   ___-____  
 
 
 
 
___-___-___
 
 
 
 
 
 
 
 
 
Date 
Post-OP Study Assessments- 6 Hours 
 
6 Hour  Post-op VNRS Pain Assessment: 
 
Is the subject able to provide VNRS Pain Assessment related to donor site pain only: 
 
 
[ ] Yes  
[ ] No     
 
Time:  ____: ____        Score : ______ 
 
Is the subject able to provide VNRS Pain Assessment related to overall pain: 
 
 
[ ] Yes  
[ ] No     
 
Time:  ____: ____        Score : ______ 
 
 
VNRS Pain Assessment recorded by: _______________________________________ 
 
Comment:    [ ] Yes  
[ ] No     
 
Comments: 
________________________________________________________________
________________________________________________________________
________________________________________________________________
________________________________________________________________
________________________________________________________________
________________________________________________________________
________________________________________________________________
________________________________________________________________
________________________________________________________________
________________________________________________________________ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
 
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Patient Initials:  __ __ __  
 
 
 
 
Page 4 of 4
 
Patient ID:   ___-____  
 
 
 
 
___-___-___ 
 
 
 
 
 
 
 
 
 
Date 
Post-OP Study Assessments- 24-Hours  
 
 
 
 
 
 
 
24 Hour  Post-op VNRS Pain Assessment: 
 
Is the subject able to provide VNRS Pain Assessment related to donor site pain only: 
 
 
[ ] Yes  
[ ] No     
 
Time:  ____: ____        Score : ______ 
 
Is the subject able to provide VNRS Pain Assessment related to overall pain: 
 
 
[ ] Yes  
[ ] No     
 
Time:  ____: ____        Score : ______ 
 
VNRS Pain Assessment recorded by: _______________________________________ 
 
Comment:    [ ] Yes  
[ ] No     
 
 
Comments: 
________________________________________________________________
________________________________________________________________
________________________________________________________________
________________________________________________________________
________________________________________________________________
________________________________________________________________
________________________________________________________________
________________________________________________________________
________________________________________________________________
________________________________________________________________ 
 
 
 
 
 
 
 
 
Patient Initials:  __ __ __  
 
 
 
 
Page 1 of 1
 
Patient ID:   ___-____  
 
 
 
 
___-___-___


 
 
 
Protocol #201400019 
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Date 
 
Follow-Up Assessment- 14-21 Days Post-op (+/- 5 days) 
 
 
Follow-Up Assessment: 
 
Date of  follow-up appointment:                  ___ / ___ / ___ 
 
Has there been any infections to the Study Donor Site area?  
 
[ ] Yes  
[ ] No     
 
Has the Therabond been completely removed from the Study Donor Site? 
 
[ ] Yes  
[ ] No     
 
Is the donor site 100% healed?    
 
[ ] Yes  
[ ] No : ______ % healed 
 
Current Treatment for Study Donor Site:      ___________________________________ 
 
Photographs taken of Study Donor Site?   
[ ] Yes  
[ ] No     
 
 
 
 
 
 
Comments: 
________________________________________________________________
________________________________________________________________
________________________________________________________________
________________________________________________________________
________________________________________________________________
________________________________________________________________
________________________________________________________________
________________________________________________________________
________________________________________________________________
_______________________________________________________________


 
 
 
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Patient Initials: 
 
 
 
 
 
 
 
Page 1 of ___ 
 
Patient ID:   ___-____ ADVERSE EVENTS 
Adverse Event # _____ 
 
AE Start Date: ___ /___ / ____  
 
AE Stop Date: ___ / ___ / ____ 
 
AE Resolved:   [  ] Yes  
[  ] No 
 
AE Type: 
[  ] AE  
[  ] SAE 
 
AE Description:_________________________________________________________________ 
 
Is this event listed on the consent form?  
[  ] Yes  
[  ] No 
 
Severity: 
[  ] Mild- Grade1 
 
 
Relationship: 
[  ] Not Related 
 
 
 
[  ] Moderate – Grade 2  
 
 
 
[  ] Possibly Related 
 
 
 
[  ] Severe – Grade 3 
 
 
 
 
[  ] Probably Related 
 
 
 
[  ] Life Threatening – Grade 4  
 
 
[  ] Related 
 
 
 
[  ] Fatal -  Grade 5 
 
 
 
Actions Taken: [  ] None 
 
 
   Clinical Outcomes: 
[  ] Death 
 
 
 
[  ] Medication Administered 
 
 
 
[  ] Recovered Baseline 
 
 
 
[  ] Additional Treatment 
 
 
 
[  ] Recovered w sequelae 
 
 
 
[  ] Withdrawn from Study 
 
 
 
[  ] Symptoms Continue 
 
 
 
[  ] Other 
 
Burn Sub-I Signature: 
___________________________________________ 
 


 
 
 
Protocol #201400019 
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Investigator Signature:  ___________________________________________ 
 
 
 
 
Patient Initials: 
 
 
 
 
 
 
 
Page 1 of _1__ 
 
Patient ID:   ___-____  
 
All medication data information will be collected and entered into an excel spreadsheet.