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10 Use ofFluorescence Guidance inBurn Surgery
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The elderly population possesses a unique burn characteristic [31]. Most burn events accidentally occur at home, frequently in a kitchen and a bathroom, owing to sluggish
alertness, decreased reaction time, and slower mobility [32].
The reduction of metabolism and the fragility of the skin contribute to the increased depth of burn extent, which consistently elevates mortality [33].
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Burn Wound Assessment
The following is a review of current modalities available to assess
burn wound depth. There are various techniques starting from
simple clinical assessment and tissue biopsy to more advanced
modalities such as thermography, ultrasound, laser Doppler imaging, and ICGA [34].
Clinical Assessment
Clinical assessment is easy, simple, and inexpensive; however,
its accuracy has signicant limitations [35]. The principle of this
method mainly depends on a subjective evaluation of wound
characteristics such as wound surface, capillary rell, and pain
sensitivity [36]. Therefore, it is possible to differentiate between
very deep and very shallow burns with decent reliability [35].
However, the clinical assessment is signicantly less accurate
for burns with intermediate depth, which was equal to 50–75%,
even though this was performed by burn experts [37–40].
Moreover, the validity of the clinical assessment was noted to be
unreliable [35]. Clinical evaluation of burn depth based on
appearance can vary between surgeons [41]. The signicant factors of this variation depend on differences in surgeon experience as well as the evolution of tissue damage that occurs in the
hours following burn injury [42, 43]. For this reason, a more
accurate burn depth assessment method is essential to aid burn
depth evaluation.
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A. Wongkietkachorn et al.
Pathological Study
Although pathologic evaluation of burn tissue is considered the
gold standard to clarify the depth of burn wounds, it is an invasive
and time-consuming method [34, 35]. Punch biopsy has to be performed on the indeterminate burn area and sent for tissue xation
with hematoxylin and eosin staining, which is later reported by
the pathologist [44]. The burn depth interpretation is identied by
the level of destruction and denaturation of cellular structures
damaged by burns [44]. Five factors are generally described to
clarify the depth of burn wounds, including collagen discoloration, intercollagen basophilic material, endothelial cell necrosis,
epithelial cell necrosis, and mesenchymal cell necrosis [45]. It is
suggested that the microvascular damage indicates a partialthickness burn, while collagen denaturation indicates a fullthickness burn [46]. Computing the most supercial patent and
the deepest blocked vessels can also increase precision [47].
Pathologic tissue study has several great disadvantages. First,
it is invasive to obtain a tissue biopsy, which may leave unnecessary scars in the supercial burn and is not practical for clinical
application [48]. Second, pathologic assessment represents structural damage of the burn tissue rather than functional loss [44,
49]. Furthermore, burn wounds can deteriorate post biopsy due to
their progressive nature [49]. Third, sampling error can occur
because the selected biopsy area may not accurately represent the
entire burn area [47]. Finally, biopsy interpretation can be subjective and requires an experienced pathologist [44].
Thermography
Thermography measures the temperature in a burn wound to
determine its depth [50]. Deep burns yield less heat than the
unburned area due to decreased blood ow to the wound surface
[51]. The accuracy of thermography has been reported to be as
high as 90% [52], but is limited by evaporative heat loss, granulation tissue, and sensitive timing [53]. These drawbacks discourage
the use of thermography after 72h from onset of injury [53].
10 Use ofFluorescence Guidance inBurn Surgery
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281
Ultrasound
Ultrasound has been proven to provide accurate burn assessment
[54, 55]. Ultrasound is operated by scanning the burn wound
structure to measure the thickness of each layer, which is divided
into the epidermis, dermis, and subcutaneous tissue [55]. However,
the ultrasound device requires its probe to be contacted with the
burn wound during an assessment. This can cause pain to the
patient. Hence, its clinical application is also restricted [55, 56].
Laser Doppler Imaging
Laser Doppler imaging (LDI) is a promising burn diagnostic tool
with few drawbacks. It is the sole modality approved by the
American Food and Drug Administration (FDA) for burn depth
evaluation [34]. Its accuracy is very high, approaching 97% with
an excellent long-term predictive ability [57]. LDI assesses the
tissue perfusion of a burn wound by detecting the red blood cell
movement and illustrates the results as two-dimensional photos
[58]. The disadvantages include the need for immobilization of
the scanned area, a long scanning time (up to 5min), and a limitation on the depth of penetration [59]. These disadvantages limit
the use of LDI.However, ICGA can solve some of these problems.
Indocyanine Green Angiography (ICGA)
ICGA works by detecting vascular perfusion within the wound area
[60, 61]. A single 0.5mg/kg dose of indocyanine green (ICG) is
administered intravenously to the patient and will bind to albumin
to form a protein complex. Then, the ICGA imaging machine can
detect the protein complex through the infrared (840–850nm) uorescence emission [62]. Percentage of maximal perfusion was
reported and can differentiate between supercial and deep burn
wounds [60, 63–65]. The cut point is the value of less than 33% and
this number represents an excellent predictive value for nonviable
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tissue [63]. Thus, an amount of greater than 33% indicates that the
burn wound is supercial [38, 63]. The accuracy of ICGA is remark-
ably better than the clinical evaluation to analyze the indeterminate
burn wounds. ICGA has been reported to provide almost 100%
accuracy in clarifying the depth indeterminate burn wounds, compared to only 50% accuracy by the clinical assessment [66]. The
number needed to treat of using ICGA was only 2 [66].
ICGA is an excellent adjunct for a burn assessment, particularly in critical areas such as the face, palms, and soles [66]. ICGA
equipment is commonly an available resource in hospitals because
of its various applications in other elds such as neurosurgery,
ophthalmology, general surgery, and plastic surgery [66].
Therefore, further use of ICGA in burn wound evaluation can be
applicable and cost-effective [66, 67].
Nevertheless, ICGA has a few limitations. First, it requires the
intravenous injection of ICG to the patient, which can be considered invasive [66]. Second, a patient who is allergic to iodine or
shellsh prohibits the use of ICGA [66, 68]. Third, there can be a
possible misinterpretation in unburned skin with intact melanin
because melanin can absorb the wavelength detected by ICGA
equipment which consequently mislead as a deep burn wound
[38, 65, 69]. Thus, ICGA must be used in conjunction with clinical evaluation.
Table 10.1 summarizes the advantages and disadvantages of
important modalities of burn assessment.
A. Wongkietkachorn et al.
Use ofIndocyanine Green Angiography forBurn
Wound Assessment
ICGA works by detecting vascular perfusion within the wound
area and has several preferable features for clinical applications
compared to other modalities: results are objective and reliable,
providing nearly 100% accuracy in the diagnosis of indeterminate
burns, compared to only 50% accuracy of the clinical assessment
[36, 60, 61, 66]. No tissue biopsy is required in ICGA, which
overcomes the weakness of the pathological study [48].
Additionally, the ICGA does not need the probe applied to the
10 Use ofFluorescence Guidance inBurn Surgery
https://t.me/medicina_free
Table 10.1 A summary of the advantages and disadvantages of important
modalities of burn assessment
Burn assessment
modalities
1. Clinical
assessment
2. Pathological
study
3. Thermography Detection of the
4. Ultrasound Scan the burn
5. Laser Doppler
imaging
6. Indocyanine
green
angiography
Method of
assessment Advantages Disadvantages
A subjective
evaluation of
wound
characteristics
Punch biopsy,
tissue xation, and
hematoxylin and
eosin staining
difference between
temperatures of
viable and
nonviable tissue
wound structure
and measure the
thickness of each
dermal layer
Assessment of
tissue perfusion by
detecting the red
blood cell
movement and
illustrating results
as two- dimensional
photos
Detecting vascular
perfusion within
the wound area
Easy, simple,
commonly
used and
cheap
Gold
standard of
burn
diagnosis
Reported
accuracy as
high as 90%
Good
accuracy,
noninvasive
Reported
accuracy as
high as 97%
with an
excellent
long-term
predicting
ability
Almost 100%
accuracy in
diagnosing
indeterminate
burns
Signicantly less
accurate for burns
of intermediate
depth
Invasive and
time-consuming
Limited by
evaporative heat
loss, granulation
tissue, and
sensitive timing
Probe contacting
to the burn wound,
which could cause
pain to the patient
Requires
immobilization of
the scanned area, a
long scanning time
which could take
as long as 5min,
and limited depth
of penetration
Requires
intravenous
injection of ICG,
contraindicated in
patients with
iodine allergy
283
wound, unlike thermography and ultrasound [53, 55, 56]. The
patient motion does not affect the working of ICGA which is
superior to laser Doppler imaging [59].
ICGA illustrates real-time imaging without the need for immo-
bilization, and its depth of penetration is 2.5cm which is suf-
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cient for scanning the entire layer of the dermis [70]. Moreover,
the number needed to treat of using ICGA is 2 [34]. However,
ICGA has some disadvantages, which are the need for ICG intravenous injection, a contraindication with iodine allergy, and a
short available period of an assessment (5–10min after injection).
However, allergy of ICGA is reported to be small [68] and
5–10min is considered adequate for recording the images of the
investigated burn area [66].
A. Wongkietkachorn et al.
Quantitative Interpretation ofIndocyanine
Green Angiography
There was a systematic review reporting the use of ICGA to evaluate burn depth in 2019 [71]. This review described the development of ICGA from animal experiments to human studies which
eventually demonstrated it as a promising tool for assessing burn
depth [71]. However, the review pointed out that there were two
major pitfalls found in these previous trials, which were a lack of
quantitative measurement when using ICGA to interpret burn
depth and the need for a comparative study focusing on indeterminate burn wounds [71]. Recently, there has been one signicant study [66] that can unlock these two signicant pitfalls. The
study disclosed the quantitative assessment and the cut point primarily in the indeterminate burn wounds [66, 72]. This prospective, multicentered, diagnostic trial showed that the accuracy of
ICGA was as high as 100.0%, compared to 50.0% accuracy in
clinical evaluation [66]. The study presented a quantitative measuring method using a percentage of maximal perfusion for
determining burn depth. Hence, the ICG angiography interpretation was precisely reproducible in the clinical setting [66]. The
percentage of maximal perfusion can distinguish a supercial
burn from the deep burn [60, 63–65]. As a result, the 33% was the
appropriate cut point [66]. The result of less than 33% was
reported to have an excellent predictive value for nonviable tissue
[63], while the number greater than 33% indicated the burn
wound to be supercial [38, 63].
10 Use ofFluorescence Guidance inBurn Surgery
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285
Use ofIndocyanine Green Angiography forBurn
Excision
During burn excision, a decision whether to excise or not excise
the area with indeterminate burn depth can be difcult [73].
Indeterminate burn wounds are dened as burn wounds that
cannot be distinguished clinically between the supercial and
deep second- degree burns. The accuracy of clinical assessment
was reported to be as low as 50–75%, even performed by burn
experts [37–40]. In some institutions, these inconclusive
wounds are debrided to decrease the morbidity, infection,
length of stays, and healthcare cost [73]. However, this management causes the patients to be operated on for unnecessary
debridement. Therefore, any adjunct modality that can provide
a more precise evaluation of indeterminate burn wounds would
be advantageous.
Although there is considerable evidence showing the potency
of ICGA for burn wound evaluation, the documentation on how
to use ICGA in burn surgery is lacking [71]. There was a recent
study that demonstrated how to use ICGA for precise wound
marking before burn wound excision [74]. A patient was
injected with 0.5mg/kg of ICG (Diagnogreen Injection; Daiichi
Sankyo Propharma, Japan). The Fluobeam 800 clinical system
was utilized, and simultaneously the wound was evaluated by
the operator.
The 33% criteria, which was previously reported with high
accuracy [66], was applied [74]. The supercial second-degree
burn appears as a bright area, while the deep second-degree burn
appears as a dark area [63, 66]. Unlike other healthy tissue, the
supercial burn wounds were hyperemic due to their pathophysiology [75]. Consequently, the percent of maximal perfusion is
signicantly different between supercial and deep burn wounds,
which aids the evaluation of burn wounds [76]. The junction of
supercial and deep areas can be marked during the application
of ICGA [74]. The ink from markers does not disturb ICGA
interpretation [74]. Eventually, the wounds can be debrided
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appropriately following the marking [74]. The demonstration of
the burn wound marking and the clinical outcomes is shown in
Video 10.1 [77].
A. Wongkietkachorn et al.
Association ofPathologic Tissue Evaluation, ICG
Interpretation, andClinical Outcomes
There is an association between pathological study, ICGA interpretation criteria, and clinical outcomes. Based on a previous study
that compared the pathological study to the ICGA objective criteria [66], ve parameters were used to determine pathologic tissue,
including collagen discoloration, intercollagen basophilic substance, endothelial cell necrosis, epithelial cell necrosis, and mesenchymal cell necrosis [45]. If these parameters were injured
greater than the midpoint of the dermis or deep skin adnexal structures were destroyed, this tissue was considered a deep burn wound
and was found to be associated with the maximal perfusion of less
than 33% in the ICGA interpretation [44, 45, 47, 61]. On the contrary, if these parameters were injured not greater than the midpoint of the dermis or there was lymphocytic inltration in the
dermis without destroyed deep adnexal structures, this tissue was
considered supercial burn wound and was found to be associated
with the maximal perfusion of greater than 33% in the ICGA interpreting criteria [44, 45, 47, 61].
The long-term wound outcomes and ICGA interpretation criteria were also investigated and yielded a 95% correction rate
[78]. If the wound had less than 33% of maximal perfusion, the
wound was found to be unhealed 21days after the injury; thus,
it should be excised [78]. If the wound had greater than 33% of
maximal perfusion, it was found to be healed within 21 days
after the injury [78].
The summary of the association between pathological study,
ICGA interpretation criteria, and clinical outcomes is illustrated
in Fig.10.1.
10 Use ofFluorescence Guidance inBurn Surgery
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Fig. 10.1 The summary of the association between pathological study,
ICGA interpretation criteria, and clinical outcomes
287
ICGA Technique forBurns
We would like to share our technique in using ICGA in burn surgery, which was supported by a prospective, multicentered,
double- blinded, interventional one group study.
Candidate fortheIntervention
Inclusion criteria required that patients be admitted to the hospital
with indeterminate burn wounds on any body area. They were
older than 18 and showed no signs of hemodynamic instability
(mean arterial pressure ≥65 mmHg, urine output of 0.5–1 mL/
kg/h, and adequate consciousness).
Exclusion criteria included an allergy to ICG and iodides, pregnancy, bleeding tendency, and psychiatric disorder. Patients are
also excluded if they have comorbidities that could impair wound
healing, such as diabetes mellitus, malnutrition, current active
infection, immunocompromised host, obesity, old age (>65years
old), and anti-inammatory medications. In addition, areas with
indeterminate wounds with scars, moles, or tattoos were excluded.
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A. Wongkietkachorn et al.
Intervention
The study ow diagram is shown in Fig.10.2. Indeterminate burn
wounds were clinically evaluated. The denition of indeterminate
burn wounds was second-degree burn wounds in which distinguishing between supercial and deep dermal extent could not be
recognized by clinical judgment alone. Supercial partial-
Fig. 10.2 Study ow diagram
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