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10 Use ofFluorescence Guidance inBurn Surgery
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thickness burns involved the supercial part of the dermis; the
wounds were erythematous and tender and usually became blistered within 24 h [79]. Deep partial-thickness burns extended
deeper into the deep part of the dermis, which contains hair follicles and glandular tissue; they were not painful unless pressure is
applied to the affected area. These wounds contained variously
mottled colorization from patchy white to red, and they did not
blanch with pressure [79].
ICGA precise marking was performed as shown in Video 10.2
[80]. A single 0.5mg/kg dose of ICG (Diagnogreen® Injection,
Daiichi Sankyo Propharma, Japan) was injected intravenously to
the patient. The Fluobeam® 800 clinical system was utilized.
Figure10.3 depicts the indocyanine green dye. Figure10.4 illustrated the use of Fluobeam® 800 clinical system in a burn patient.
The room’s lights were turned off during the procedure. The
viewer of the machine was held approximately 30cm perpendicularly to the wound. It took 5–10seconds after the injection for the
image to appear on the monitor, and the illustration of ICGA on
the monitor lasted approximately 5–10min per single injection.
Fig. 10.3 Indocyanine green dye. (Diagnogreen® Injection, Daiichi Sankyo
Propharma, Japan) was injected intravenously
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A. Wongkietkachorn et al.
Fig. 10.4 The Fluobeam® 800 clinical system
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The Fluobeam® 800 clinical system was approved by the US Food
and Drug Administration (FDA), and its penetrating depth was
reported to be 2.5 cm, which was adequate to evaluate the full
thickness of the skin [62, 70].
ICGA Objective Interpretation Criteria
Thirty-three percent of maximal perfusion was applied as a cut
point between supercial and deep second-degree burns [60, 63–
65]. Fig. 10.5 depicts the objective interpretation of
ICGA. Supercial second-degree burns were dened as burns
with maximal perfusion of more than 33% that were bright and
diffuse, showing patency of small vessels of the subpapillary and
dermal plexuses [38, 63]. Deep second-degree burns were dened
as burns with maximal perfusion of less than 33% or the dark area
yielding mottled yet diffuse uorescence showing partial patency
of the dermal plexus [38, 63]. As a result, the deep second-degree
burns were methylene blue-painted to determine the area to be
excised in the operating room.
Following the ICGA, the painted wounds, which were deemed
to be deep burn wounds, were excised and covered with skin
grafts. Five days following the operation, the grafted area was
checked for wound closure. Unmarked areas, which were consid-
Fig. 10.5 How to objectively interpret ICGA.The blue arrow indicates 33%
of maximal perfusion as a cut point between supercial and deep seconddegree burns
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A. Wongkietkachorn et al.
abc
Fig. 10.6 An example of ICGA precise marking results. (a) ICGA precise
marking, (b) excision along the marking, (c) skin graft placement
a
Fig. 10.7 An example of ICGA precise marking results. (a) Five days after
the operation to conrm the complete wound closure. (b) The unmarked area
was measured on post-burn day 21 to determine the complete wound closure
(c) The patient wound was followed up at 2months after the injury
b
c
ered supercial burn wounds, were covered with silver-contained
hydrober (Aquacel® Ag+Extra™; Convatec, UK). On post-burn
day 21, the unmarked region was measured to evaluate complete
wound closure, which also conrmed the supercial nature of the
wounds. All wounds were followed up at 2months after the injury.
Figures 10.6, 10.7, 10.8, and 10.9 illustrate an example of
ICGA marking accuracy. The summary of the ndings is shown in
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abc
Fig. 10.8 Another example of ICGA precise marking results on the right
hand. (a) ICGA precise marking, (b) excision along the marking, (c) skin
graft placement
abc
Fig. 10.9 Another example of ICGA precise marking results on the right
hand. (a) Five days after the operation to conrm the complete wound closure. (b) The unmarked area was measured on post-burn day 21 to determine
the complete wound closure (c) The patient wound was followed up at
2months after the injury
Table10.2. Using ICGA precise marking, the overall rate of shortterm complete wound closure, which included both supercial
and deep burns, was reported to be as high as 96.7% (29/30). This
high rate of complete wound closure was signicantly higher than
the expected rate of 80%, p = 0.01. The long-term complete
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Table 10.2 Summary of results
Wound closure on Day 5
Wounds
Supercial
group
Deep group 12 12 >0.999
Overall 29 30 >0.999
or day 21
17 18 >0.999
A. Wongkietkachorn et al.
Wound closure at
2months P-value
wound closures at 2months conrmed the short-term result and
achieved 100% of complete wound closure. There were no signicant differences between the short-term and long-term wound
closure rates (p>0.999).
Post hoc analysis was conducted. In the supercial group, the
short-term complete wound closure rate was 94.4% (17/18), while
the long-term complete wound closure rate at 2 months was
100.0% (18/18). There was no signicant difference between
short-term and long-term wound closures (p > 0.999). On the
other hand, the deep burn achieved both short-term and long-term
complete wound closures of 100% (12/12). There was also no difference between short-term and long-term wound closures
(p>0.999).
Discussion
Interpretation
The study demonstrated that employing ICGA precise marking to
guide indeterminate burn excision led to a remarkable rate of
complete wound closure. In some centers, indeterminate burns
were early excised, with deep burns to prevent infection and
encourage early wound closure [81]. In our study that included 30
indeterminate burns, it was found that 18 (60%) were supercial
second-degree burns. Up to 94.4% (17/18) healed within 21days
without any need for excision. This demonstrates the benet of
ICGA in sparing tissue areas. If the wound is located in a critical
area, such as the face, hand, sole, or joints, ICGA could signicantly save the patient’s function.
10 Use ofFluorescence Guidance inBurn Surgery
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The intervention occurred as early as 2.4days. This clearly shows
the advantage of employing ICGA in indeterminate burns. One of
the obstacles found in burn excision was that the indeterminate burn
made surgeons delay the surgery for the well-dened depth of the
wound [82, 83]. Moreover, the debridement of indeterminate burn in
the early phase could also result in unnecessary excision of the viable tissue if the tissue was later found to be supercial burn [84].
Utilizing ICGA precise marking has the further benet of allowing
for the minimally invasive excision of indeterminate burns and the
safe early debridement of other distinctive types of wounds, including deep second and third burns. The skin graft could be applied
after the excision, while the other supercial parts of the wound
would heal in 21days. This adequate and precise surgery not only
helps burn patients to get cured faster but also helps them begin
rehabilitation, recover function, and get back to work quicker [85].
The slight difference between short-term and long-term wound
results revealed that the ICGA precise marking procedure could
promote quicker wound healing with persistent results. Without
using ICGA, some deep burns may recover in the short term, but
later on could progress to unstable scars, as such the wound may
become weak and trend to recur [86]. Consequently, this difculty
may require further wound dressings or even secondary surgery
and closure with a skin graft [86, 87].
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The Appropriate Time toPerform ICGA Marking
The appropriate time for ICGA marking is important. This study performed ICGA about 2.4days following injury. First, the patients gain
more benets if the ICGA is performed early, and patients could have
earlier excision than the standard treatment. Conventionally, surgeons
need to wait for the indeterminate wound to become more distinct as
either supercial or deep burn before making excision because the
features of the wound (supercial or deep) become more signicant
when the wound is clinically assessed late [36]. Second, ICGA
should be conducted on the day that the patient is sufciently stable
to undergo further early excision. Commonly, it was reported that the
time of early excision was within 1–6days [88]. The mean of 2.4days
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in this study was suitable in the 6-day limit [88]. Third, performing
ICGA at a single time point in the rst 5days after burn injury is sufcient to differentiate between supercial and deep burn [65]. There
was a case series that the ICGA was conducted daily on the burn area
for the rst 5days after burn injury [65]. It was found that the percent
of perfusion changed over time, but the difference between supercial and deep burn was still obvious [65].
A. Wongkietkachorn et al.
The Importance ofAdequate Measurements
forComplete Wound Closure
This study examined complete wound closures at two time periods,
including short-term and long-term assessments, to be appropriately characterized as complete wound closure in the global standard and utilized in future analytical studies [89]. The US Food and
Drug Administration (FDA) currently denes complete wound closure as achieving 100% epithelialization without drainage or dressing requirements conrmed at two consecutive study visits at least
2weeks apart [89]. A literature review that studied healing rates of
chronic wounds found that among 53 RCTs and comparative studies that assessed wound closure, 19 (35.8%) studies did not adequately dene complete wound closure [90]. It was suggested the
widespread adoption of a standard complete wound closure denition would allow more robust comparisons of treatment effects
across studies to improve the evidence base and enhance the treatment decision-making process in clinical practice [91]. This study
measured the short-term complete wound closure at 5 or 21days
and the long-term measurement at 2 months, which was greater
than the minimum requirement of 2weeks. As a result, the study
ndings were adequately dened as complete wound closure.
Passing Through theDiculty ofHow toMark
theBurn Wounds
The most complex challenge in the study, and one that deserves
attention, was how to mark the burn wounds. Conventionally, the
surgical wound or skin is marked with the commercial marking pen
10 Use ofFluorescence Guidance inBurn Surgery
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or gentian violet [74]. However, there were a lot of obstacles if the
conventional marking method was used to mark the burn wounds.
First, the tip of the commercial pen was hard and could cause pain
during the marking when the pen’s tip was pressed to the burn
wound. Second, the commercial ink and gentian violet were easy to
be erased when facing with the nature of the burn wound, which
could produce secretion, and when contacting with the ointment of
the dressing. Third, the tip of the pen may cease functioning after a
few inches of marking because of the secretion of the wound or the
remnant of dressing ointment obstructing the tip of the pen. These
were obstacles to the conventional method of burn wound marking.
There were a lot of attempts to solve the pain and easy-to-erase
problems. The majority of the available markers were purchased
and appraised. Aside from the markers’ brands, several techniques
of marking were also tested. A number of different brush sizes
were sterile and examined, which might be an ideal match. Finally,
it was discovered that using methylene blue as the ink and a sterile
cotton bud as the painting instrument was the easiest and simplest
technique that could be generalized throughout several hospitals.
These two materials already are available in most hospitals.
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Generalizability
Using ICGA is simple, which makes it appropriate to be generalized.
The 33% of maximal perfusion cut point utilized is objective interpretation, which is uncomplicated to reproduce [66]. The described
study was also among the very few studies [63, 66, 71, 76, 92], in
which the objective criteria were applied in executing
ICGA.Supercial and deep burn wounds are signicantly different
and simple to distinguish using ICGA [76] because the supercial
burns tend to have a high perfusion area due to vasodilatation caused
by an inammatory response in the pathophysiology of burns [76, 92,
93]. In addition, the described study only included second-degree
burns, whose pathophysiology consisted of partial dermal injury
where venous drainage was not signicantly involved [94]. The high
intensity in burn may not be restricted in the same way with using
ICGA in ap reconstruction, which high perfusion could be a sign of
venous congestion and may progress to ap necrosis [95].
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Limitations
Some conditions limit the use of ICGA.Firstly, ICGA requires
the injection of indocyanine green. Although the allergic rate of
ICGA was low [68], the use of ICGA precise marking in patients
with iodine allergies is contraindicated. Secondly, the availability
of the ICGA investigating period is 5–10min after injection. The
team needs to be well prepared for this limited time of the investigation, which was found to be adequate to perform precise
marking. If the time runs out, an additional injection with the
similar dose could be achieved. Thirdly, ICGA is limited in some
areas of the body. ICGA generates pictures by detecting infrared
(840–850nm) uorescence emission from the complex of albumin and ICG [62]. Any obstacles such as hair, tattoo, and mole
could block the interpretation of ICGA and, therefore, were
excluded in this study. Lastly, the marking requires a short learning curve of two to three cases because of the eye-hand coordination between the real marking and the ICGA monitor. Nevertheless,
the marking is simple, and the marking’s outcomes are worth the
price of the practice.
Regarding the use of the ICGA, there seems to be minimal
uncertainty in the diagnosis of remaining indeterminate burns.
This is evidenced by the supercial burn wound that did not
heal within 21days, as conrmed by the ICGA. The explanation might lie in the ICGA interpreted cut point. It was discovered that the diagnostic of ICGA had a gray zone in indeterminate
areas between 25% and 45% of maximal perfusion [63]. The
use of 33% cut point was suggested to handle this problem [63]
and was selected for this study. The 33% cut point was found to
yield as high as 88% positive predictive value of removing nonviable tissue and as low as 16% negative predictive value of
removing viable tissue [63]. Furthermore, the overall rate of
short-term complete wound closure reported was 96.7%, which
demonstrates that this cut point delivers favorable results but is
not awless. Further research should explore more on the diagnostic criteria used in interpreting ICGA in burn to perfect this
method.
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