Phẫu Thuật Bỏng: Tiếp Cận Và Phương Pháp Điều Trị Từ Trung Quốc (Chinese Burn Surgery)

342
There are pathological processes and mechanisms of
occurring diseases that are more complicated than those of
the single injury. There are also theoretical bases and techni-
cal methods for diagnosis and treatment to be based upon.
The term “combined effects” seems to be generalizing
and sweeping, but we believe that we should emphasize the
study of both the aggravating effects and the reducing effects
of combined injury, and studying the material factors and
molecular adjustment, which are transformed from these dif-
ferent effects; namely, the material bases and adjusting
mechanism of the either aggravating or reducing effect that
occurs. If these important problems had been expounded, the
essential theoretical cognition of combined injury would be
deepened, which would actively support and use the reduc-
ing factors to antagonize and eliminate the aggravating fac-
tors, thereby putting forward new notions, methods, and
measures for prevention and treatment.
Combined effects manifest on different levels, including
in the whole body, organs, tissues, cells, and ultrastructure,
which are mentioned briefl y in the following.
13.7.1 Combined Effects of the Whole Body
During the radiation injury combined with a burn, the com-
bined effects of the whole body were mainly and centrally
refl ected in the fatal effect, and was concerned with the irra-
diation dose that caused the same fatal effect; when the wound
condition was beyond the middle degree, the mortality after
combined injury often exceeded the sum of the two single
injuries. For example, the mortality of dogs with 25 % deep
second-degree burns of the body surface was 12 %. There
were no deaths in the dogs after irradiation with 100-roentgen
X-rays alone, but the mortality of the combined injury of both
was 75 %. When using the regression calculation, the LD 50
irradiation dose of the dog was 2.34 Gy, which was 1.41 Gy
after a combined 20 % surface area burn (deep second-degree
and light second-degree are 50–50), and after a 30 % surface
area combined injury it was 1.18 Gy; namely, the LD 50 dose
of this type of combined injury was only equal to 50–60 % of
the LD 50 dose in radiation sickness alone. Comparing 169
dogs with radiation–burn in a nuclear explosion with dogs
with radiation sickness alone by irradiation with the same
doses, the LD 25 , LD 50 , and LD 75 of the former were 63, 70,
and 75 % of the latter respectively (the approximate number
was 60–75 %).
Combined effects showed different manifestations at dif-
ferent courses and different stages, and they manifested most
evidently at the terminal stage. Also, combined effects did not
appear to be all the same in different organs, tissues, and cells.
Research into the hematopoietic tissues, serum, abdominal
lavage fl uid, intestinal epithelium, adrenal cortex, and mito-
chondria of liver cells was more frequent and deeper.
13.7.2 Combined Effects of Hematopoietic
Tissues
By several nuclear tests and the research in the laboratories,
we found that the characteristics of combined effects in
hematopoietic tissues after radiation–burn were as follows:
the function of hematopoiesis during radiation injury was
inhibited, damaged, and was more and more serious with the
increase in irradiation doses; during burn injury the slight
damage was the reaction of stimulation, while the severe
damage showed a reaction of inhibition. The reaction of
stimulation in the slight burn injury was to a certain extent
compensation for the inhibition of the radiation injury, thus
causing the extent of damage in radiation–burn to be more
severe than that in the burn injury and slighter than that in the
radiation injury. When the burn injury reached a certain
severe extent, this caused the hematopoietic function, which
had been damaged by radiation injury, to be further destroyed,
and to be a failure ahead of time (void), which reduced the
irradiation dose for complete inhibition of the regeneration
of hematopoiesis, and decreased the rate of regeneration. In
the most severe wound conditions after combined injury the
extent of damage manifested as an aggravating effect, which
was greater than that of the sum of the two single injuries
(1 + 1 > 2). The damage to the erythrocytic system was more
serious than that to the granulocytic system. From the view
of the rat experiments, the biological effect of whole-body
irradiation with 6 Gy was greater than that of the 15 % third-
degree burn injury. After combining the two injuries, the bio-
logical effect was obviously more severe than that of the two
single injuries (1 + 1 > 1), and was also greater than that of the
sum of the two single injuries (1 + 1 > 2).
The results of the combined effects in the nuclear test on
372 dogs showed that the maximum doses of complete inhi-
bition of the hematopoietic regeneration in hematopoietic tis-
sues, such as bone marrow, spleen, and lymph nodes, during
acute radiation sickness alone and radiation–burn were
reduced from 6.7, 7.0, and 9.5 Gy in radiation alone to 5.0,
5.0, and 7.0 Gy in radiation–burn respectively, i.e., reduced
by 23, 29 and 26 % respectively. When irradiating within the
dose range of 4–5 Gy (the main dose range of demand at the
time and for possible treatment), the rates of regeneration of
hematopoiesis in the bone marrow, spleen, and lymph nodes
in radiation alone were 62, 82, and 84 % respectively, while
in radiation–burn they were reduced to 13, 15, and 60 %
respectively. These combined effects were refl ected mainly
in the stem cells and young cells, which have the ability to
divide, the cells younger than the neutrophilic myelocytes
were signifi cantly decreased. As for the targets of the number
of mitotic divisions of the bone marrow, the proportional
number of cells younger than the polychromatic normoblasts,
and the number of megakaryocytes, the decreasing extent in
radiation–burn were greater than that those of the sum of the
13 Combined Radiation–Burn Injury

343
two single injuries (1 + 1 > 2). After the dogs and rats with
radiation injury were subjected to a combined 15 % second-
degree burn, the micronuclear development rate of lympho-
cytes showed no evident difference from that in radiation
alone. Moreover, during radiation–burn a great many leuko-
cytes were consumed at the wound surface or in the wound,
and accumulated at the vascular beds of the viscera, and there
was heavy hemorrhage, which would doubtlessly increase
the consumption of blood cells and decrease their number.
13.7.3 The Combined Effects of Serum
of Injured Animals
on Hematopoietic Cells
13.7.3.1 The Effects of Serum in Radiation–Burn
on the Formation of CFU-E and BFU-E
in the Erythrocytic System
of Bone Marrow
Using whole-body irradiation with 12 Gy by 60 Co γ-rays
combined with illumination with a 5-kW bromo-tungsten
lamp caused a 30 % total body surface area (TBSA) third-
degree burn on the back of rats as a model. Three, 12, 24, 48,
72, and 96 h after burn injury alone, all the CFU-E were
clearly higher than those in the normal control groups
( p < 0.01), they were 1.58–3.84 times higher than those in the
normal control groups, in which it reached the highest value
at 24 h after injury, which was 342.8 % of the normal control.
Twelve and 48 h after injury the values were 279.5 and
264.3 % respectively, while after 72 h, it had somewhat
reduced, but after 96 h it was still 157.8 %. Three, 12, 24, 48,
72, and 96 h after radiation–burn, although they were lower
than in the burn only group, the CFU-E values were still
markedly higher than those in normal control groups
( p < 0.01), namely 166.8, 203.4, 252.4, 197.3, 166.3, and
135.2 % respectively, which clearly showed the stimulating
hematopoietic effect. When adding the serum of rats with
radiation injury in vitro, there was a distinct inhibitory effect,
with only a few CFU-E colonies growing, and in some cul-
ture media no CFU-E colonies were observed. In the 24-h
group the number of colonies was the highest, but still only
12.7 % of that in the normal control group ( p < 0.01), even
lower than that in the burn only group and the radiation–burn
group ( p < 0.01). The changing trend of BFU-E was the same
as for CFU-E. The most prominent stimulating effects of the
serum in radiation–burn were at 12, 24, and 48 h after injury,
i.e., 179.4, 205.1, and 175.3 % respectively. In the burn
injury alone group, they were as high as 215.6, 261.6, and
203.3 % in the burn injury only groups, but they were only
10.9, 12.5, and 10.3 % in the radiation injury only groups,
which were evidently lower than those in the normal control
groups and radiation–burn groups ( p < 0.01), and even lower
than those in the burn only groups ( p < 0.01).
13.7.3.2 The Effects of Serum in Radiation–Burn
Injury on the Formation of CFU-GM
in the Granulocytic
System of Bone Marrow
Three, 12, 24, 48, 72, and 96 h after burn injury alone, the
numbers of CFU-GM colonies were 147.6, 200.8, 228.4,
183.8, 183.6, and 120.9 % of those of the normal control
groups respectively. Compared with the normal control
groups, the difference between them was distinct ( p < 0.01).
In the six time phase groups of radiation–burn they were
120.7, 151.1, 174.2, 150.9, 119.8, and 113.2 %, which were
clearly higher than those in the control groups. In particular,
in the 12-, 24-, and 48-h groups after injury the difference
was very distinct ( p < 0.01). However, when adding the
serum of rats with radiation injury in vitro, only a few
CFU-GM colonies grew, only 11.3 % of that of the normal
control group in the longest time phase.
The results mentioned above showed that the serum after
radiation–burn had an evidently promoting effect on the
hematopoiesis of the erythrocytic and granulocytic systems
of bone marrow, while the effect was weaker than that in the
burn injury alone group; the serum of the radiation injury
group had a distinctly inhibitory effect. Examining the
amount of TNFα and IL-6 in serum proved that the levels of
the two cellular factors were higher than those in the normal
control group and radiation injury group, but lower than that
in the burn injury alone group; analyzing the condition indi-
cated that this was probably the result of the comprehensive
action of the promoting effect in burn injury and the inhibi-
tory effect in radiation injury.
13.7.4 The Combined Effects of Abdominal
Lavage Fluid After Injury
on the Hematopoietic Cells
13.7.4.1 The Effect of Abdominal Lavage
Fluid on the CFU-E of Erythrocytic
Progenitor Cells of Bone Marrow
The rats underwent whole-body irradiation at 12 Gy by 60 Co
γ-rays combined with a 30 % TBSA third-degree burn injury.
The abdominal lavage fl uid was drawn aseptically 3, 12, 24,
48, and 72 h after injury, then cultured with erythrocytic cul-
ture medium of bone marrow with added protein (40 μg/ml).
We found that 3, 12, 24, 48, and 72 h after burn injury alone,
all the CFU-E values were higher than those in the normal
control groups ( p < 0.01). They reached 175.1, 192.3, 215.7,
187.3, and 183.5 % of the normal control respectively, and
was the highest 24 h after injury. Three, 12, 24, 48, and 72 h
after radiation–burn, they were 133.3, 162.1, 188.1, 160.6,
and 139.2 % respectively, a little lower than those in the burn
only groups, but clearly higher than in the normal control
group ( p < 0.01), all of which showed a distinct effect of
13.7 On the Combined Effects of Radiation–Burn

344
stimulating hematopoiesis. However, after adding abdominal
lavage fl uid of the radiation injury, only a few CFU-E colo-
nies grew. Even when the number of colonies was the highest
at 24 h, it was still only 1.6 % of value for the normal control
group ( p < 0.01), and even lower than in the burn only group
( p < 0.01) and radiation–burn group ( p < 0.01).
13.7.4.2 The Effect of Abdominal Lavage Fluid
on the BFU-E of Erythrocytic Progenitor
Cells of Bone Marrow
Three, 12, 24, 48, and 72 h after burn injury, the number of
BFU-E colonies were 165.3, 181.6, 202.3, 174.9, and
171.7 % of the normal control respectively, all of which were
higher than in the normal control groups ( p < 0.01). Three,
12, 24, 48, and 72 h after radiation–burn, the values were
110.8, 120.3, 147.7, 119.4, and 116.2 % respectively; in the
groups 12, 24, and 48 h after injury, they were increased
most clearly ( p < 0.01). In the radiation injury group, we
observed growth of only a few BFU-E colonies, e.g., in the
group 24 h after injury it was only 2.6 % of the value of the
normal control group.
13.7.4.3 The Effect of Abdominal Lavage Fluid
on Granulocytic Progenitor Cells
of Bone Marrow
Three, 12, 24, 48, and 72 h after a 30 % third-degree burn
only injury, the numbers of CFU-GM colonies were 161.9,
218.9, 241.2, 199.8, and 176.2 % of the normal controls
respectively; they were signifi cantly higher than those in the
normal control groups ( p < 0.01). In the fi ve time phase groups
3, 12, 24, 48, and 72 h after burn injury, they were 139.6,
186.4, 204.6 163.7, and 156.1 % of the normal controls, also
clearly higher than in the control groups ( p < 0.01). When
adding abdominal lavage fl uid of rats with radiation injury,
we also observed growth of only a few CFU-GM colonies.
The results mentioned above showed that the effects of
abdominal lavage fl uid of rats on the hematopoietic function of
the erythrocytic and granulocytic systems of bone morrow and
on the serum were fundamentally the same, which indicated
that after burn injury and radiation–burn, abdominal lavage
fl uid had the signifi cantly promoting effects on the erythrocytic
and granulocytic systems of bone marrow, while abdominal
lavage fl uid of the radiation injury showed a clearly inhibitive
effect; these effects may have something to do with the changes
in the level of cellular factors in the peritoneal cavity.
13.7.5 Combined Effects of Intestinal
Epithelium
The information from the effect of the nuclear test on ani-
mals showed the threshold dose of intestinal type of radia-
tion injury that occurred in dogs was 8.6 Gy for radiation
injury alone, and 6.8 Gy for combined injury (reducing about
20 %), within the crossing dose range of the intestinal type
and bone marrow type, most of the types in the single radia-
tion sickness group were of the bone marrow type, while in
radiation–burn, most of them were of the intestinal type.
In experiments with mice, using 8 and 8.5 Gy whole-body
irradiation (causing very severe bone marrow type), using
12, 15, and 16 Gy whole-body irradiation (causing light
intestinal type) and using 18, 20 and 26 Gy whole-body irra-
diation (causing severe intestinal type), eight doses were
used in all, and they were combined with 15 % third-degree
burns; or using 12 Gy whole-body irradiation combined with
5, 10, 15, and 25 % third-degree burn. After systematic study,
we put forward the dose–effect data between the injurious
factor dose of radiation injury and radiation–burn and the
effect of intestinal epithelium as follows:
1. In using 12 Gy combined with 15 % third-degree burn
injury, the combined effects showed obvious stages of the
disease course. There appeared to be two death peaks in
radiation–burn: one was within 48 h post-injury, where
the animals mainly died from shock; the other peak was
within 72–96 h, which appeared to be similar to the death
peak in radiation only injury.
2. The irradiated dose needed for the number of intestinal
crypts regenerating to 50 % of the normal value 72 h after
injury (the regenerating stage of the intestinal epithe-
lium), it was 12.4 Gy in the radiation only group; it
increased to 15 Gy in the radiation–burn group, which
increased by 2.6 Gy, the dose-modifying coeffi cient
(DMF) was 1.21.
3. In the small intestine 72 h post-injury, the incorporated
dose of 3 H-TdR for the radiation only group was
Y = –5809.44 + 162770/X, r = 0.9980; and for the radiation–
burn group, it was Y = 52028.3-16054.2 lnX, r = 0.9884.
The incorporated dose of 3 H-TdR (Y) showed a signifi cant
negative correlation with the irradiated dose (X).
4. Using 12 Gy combined with different burn surface per-
centages (X) and an incorporated dose of 3 H-TdR (Y)
showed Y = 16219.5 X 0.413 , r = 0.9987; the relationship
between them was quite marked.
5. After irradiation with 8 and 12 Gy, the incorporated dose
of 3 H-TdR of the small intestine clearly increased, com-
bined with a 15 % burn injury the effect was not clear, but
at that moment the villi of intestine shortened markedly.
6. Counting the decreasing number of crypts and incorpo-
rated dose of 3 H-TdR, corresponding to the percentage of
normal controls when increasing 1 Gy at each time point
in every irradiation dose group, within the range of
12–16 Gy irradiation doses, the number of crypts
decreased by 3–10 %, the incorporated dose decreased by
5–10 %, while in the range of 18–26 Gy irradiation doses,
the number of crypts only decreased by 0.01–1.5 % and
the incorporated dose only decreased by 1–2 %.
13 Combined Radiation–Burn Injury

345
The results mentioned above showed that there was a def-
inite dose–effect relationship between the injurious factor
and the effect of the intestinal epithelium in radiation injury
and radiation–burn and the changing trends in both injuries
were identical. There were signifi cant differences in the
dose–effect of the intestinal epithelium in radiation injury
among the extremely severe bone marrow type, the light
intestinal type, and the severe intestinal type and the corre-
sponding types of radiation–burn. The burn injury of less
than a 25 % third-degree burn had a promoting effect for the
regeneration of the damage to the intestinal epithelium
induced by 12–16 Gy. The stem cells of the intestinal epithe-
lium were damaged, but some stem cells still remained,
which was the prerequisite for the promoting effect being
realized. However, when irradiation with 1,826 Gy was car-
ried out the stem cells of the intestinal epithelium were all
lost; thus, there was no distinct difference among the differ-
ent doses and radiation–burn.
In addition, whether the homogenate supernatant of the
intestinal mucosa under different treatments promoted repair
of the intestinal epithelium after irradiation injury was stud-
ied by using cell culture of the intestinal epithelium and the
technique of 3 H-TdR incorporation. We found that the
homogenate supernatant of the intestinal mucosa of normal
animals had an clear promoting effect on the epithelial cells
of the intestine, but the promoting effect of the same homog-
enate supernatant of burned animals was stronger (compared
with the normal animals, p < 0.05), while the homogenate
supernatant of the intestinal mucosa of the animals irradiated
with 12 Gy only did not promote repair of the intestinal epi-
thelium. The experiments also found that the secretory prod-
uct of the submandibular gland (which may be epithelial
growth factor [EGF]) had a promoting effect on the repair of
the intestinal epithelium, but the secretory product may be
fi ltrated with dialyzer (the intercepting amount was 10,000–
15,000). This indicated that the promoting repair factor of
intestinal epithelium produced or increased after burn injury
was the important material basis for promoting repair of the
intestinal epithelium in radiation–burn. This material factor
is something whose existence in the homogenate supernatant
of the intestinal mucosa is entirely possible in addition to
EGF, its molecular weight is greater than 15,000, it retains
some of its activity after heating, and it is a substance with no
distinct species specifi city in rats, mice, guinea pigs, and
rabbits.
From the results of the above research we found that to a
certain extent burn injury can promote regenerative repair of
the intestinal epithelium in radiation injury from the com-
bined effects, and from the studying mechanism it proves
that there is a material factor that can promote repair of the
intestinal epithelium. From an application perspective, it
reveals a new way of fi nding a promoting repair factor for the
intestinal epithelium.
13.7.6 Combined Effects of the Adrenal Cortex
After using whole-body irradiation for dogs with 4 Gy com-
bined with 20 % burn injury (third-degree 8 % + second-
degree 12 %) and whole-body irradiation for rats with 5.5 Gy
combined with 15 % third-degree burn injury, the hyperfunc-
tion of the adrenal cortex was found in both single injuries
(burn only and radiation sickness only) and radiation–burn.
The clear cells of the cortex that transferred to the dense cells
developed markedly; the chemical basis of the cells was the
reduction of vitamin C, cholesterol, and lipids, while the
amount of phosphatase and RNA increased. The changes in
the cortisol in serum and in the free cortisol in the urine of
the dogs, and the pathological changes in the hyperfunction
of the adrenal cortex in rats showed that the extent of changes
in radiation–burn was greater than those in the two single
injuries, but less than the sum of the two single injuries (i.e.,
1 + 1 < 2), which was considered to be the characteristics of
the combined effects of the adrenal cortex. It may be because
the stress reaction (hypersecretion) after the two injuries
combined was greater than in the single injury, and the extent
of hyperfunction was controlled by the damaged tissue
(degeneration and necrosis of the cortical cells).
When discovering the hypersecretion of the adrenal cor-
tex, there appeared to be a “mitochondria-lipid bubbles-
lysosome- smooth endoplasmic reticulum complex” in the
cortical cells. Under the optic microscope they appeared as
an eosinophilic mass the single cortical cell, even a cluster of
the cells entered into the blood sinuses, which was called
“cytoplasm of cortical cells and the cells entering sinuses.”
These changes proved to be the specifi c way of strengthening
hormone release.
13.7.7 Combined Effects of Liver Mitochondria
After using whole-body irradiation for rats with 6 Gy com-
bined with a 20 % third-degree burn injury, the cristae of
the inner membrane of the liver mitochondria were broken,
formed cavitations, the controlling respiratory rate of mito-
chondria was reduced, the total amount of adenosine mono-
phosphate in liver did not change, but the amount of ATP
was reduced, and the extent of the reduction of ATP in
radiation–burn was greater than that in a single injury; thus,
the change in loading energy was serious. When determin-
ing the changes in lipid peroxides (LPOs) of the liver mito-
chondria, vitamin E, the sulfhydryl group, cytochrome C
oxidase, and controlling the respiratory rate, phosphor and
oxygen ratio, etc., we found that the causes of the rapid
reduction of lipid peroxidation in radiation–burn, which
were related to the indirect action of irradiation, were LPOs
in the burned skin releasing into the blood, complements
activated after injury, leukocytes releasing free radicals, the
13.7 On the Combined Effects of Radiation–Burn

346
reduced amount of anti-oxidants, etc.. The reduction of
respiratory function and enzyme activity had a certain rela-
tionship with the lipid peroxidation damaging the mito-
chondrial membrane.
During research into the effects of the breaking down
of the product of burn eschar on the damage of mitochon-
dria, and contrasting with the extract from normal skin,
we found the extract from the burn eschar had a clear
inhibitory effect on the normal mitochondrial respiration
of the liver, the characteristic was that the fourth (IV)
state of mitochondrial respiration was increased, which
indicated partly getting out of the coupling reaction
between the oxidation and phosphorylation. This may be
the cause of breakdown of the synthesizing ATP in
mitochondria. .
Moreover, the change in cyclic nucleotide, which had an
important effect on the hormone action and metabolism,
also showed signifi cant meaning. After using whole-body
irradiation with 4 Gy combined with a 20 % burn, the ratio
of cAMP/cGMP in serum was markedly higher than that
before injury; the peak value on the second day was 3.4–4.3
times that before injury. It was 3.05–3.45 times the value at
the same stage in the radiation only injury, and two times the
value in the burn injury alone; it was clearly higher 12 h
after radiation–burn than in radiation injury only, and it was
signifi cantly higher after 3 days than in the burn injury
alone. Thus, we consider that this may be related to the fac-
tors of the stress reaction affecting the activity of adenosine
monophosphate cyclase and phosphodiesterase and related
to the tissue damage.
13.8
Diagnosis and Comprehensive
Treatment for Radiation–Burn
13.8.1 Diagnosis of the Condition of the Injury
Radiation–burn is an injury that is formed by combining a
burn injury with radiation sickness, the diagnosis of which
should be based on comprehensive judgment of a single
injury. The burn on the body surface is easy to observe,
while the diffi culty in diagnosing a combined injury lies in
fi nding out whether it is combined with radiation injury
and visceral injury. According to the principles of grading
diagnosis and grading treatment, the key point for diagno-
sis in infl icted area is mainly to fi nd out whether the injury
is harmful to the patient’s life; the key point of diagnosis
for organizing early treatment is to place stress on distin-
guishing the wounded, who enjoy priority treatment, to
examine all aspects, and making a defi nite diagnosis of the
combined injury is generally completed in the medical
reserve units in the rear.
13.8.1.1 Appraisal of the Types and
Conditions of the Injury
1. The ratio of the combined injury occurring in the subjects
exposed to nuclear weapon injury was about 40–50 %
from the air, and about 50–80 % on the ground. The ratio
of combined injury was greater in the explosion of a small
nuclear weapon than that in the explosion of a large nuclear
weapon. The single injury in the explosion of a nuclear
weapon above the medium type was mainly a burn injury
alone, while that in the explosion of a small type nuclear
weapon was mainly acute radiation sickness alone.
2. Radiation–burn occurring in exposed subjects was usu-
ally more severe in a small nuclear weapon on the ground,
while in a large nuclear weapon in the air, the main kind
of injury was a burn–blast combined injury.
3. Combined injury occurring under concealed conditions
(fortifi cations, large weaponry, buildings, etc.) consisted
mostly of the indirect blast injury and fl ame burn injury,;
sometimes there would be radiation–burn.
4. The ratio probability occurred under different conditions
of nuclear weapon injury: light injury accounted for about
50–65 %; medium injury for about 15–20 %, and severe
injury and above for around 20–30 %. If towns were
attacked by nuclear weapons without any preparation, the
ratio of severe injury would be much higher.
5. Analyzing the rules of the injury part occurring in the
wounded may be benefi cial to organizing treatment,
which would provide evidence for calculating operation
capacity and the beds for the subjects admitted. According
to the data analysis data of a nuclear explosion in Japan,
the incidences of the wounds on the head and neck, upper
extremities, and chest were relatively higher.
13.8.1.2 The Initial Diagnosis
in the Infl icted Area
Saving the injured and sending them to the rear in the infl icted
area are required to understand the conditions of the injury. It
is impossible to inquire about and examine the wounded in
detail because of the conditions at that time; thus, we have to
obtain the fi rst impression of the wounded by observing the
general condition as far as possible and to tell from their
appearance if they have any wounds or burn injury, before
deciding the extent of the wound, to judge whether the
wounded were contaminated by radiation or by radiation–
burn upon brief inquiry. According to the rescue and treat-
ment tasks in the infl icted area, the most important and urgent
matters are to fi nd out whether there are wound conditions
that might endanger the subjects’ lives, to judge the poor
prognosis, and to fi nd out the endogenous cause so that the
wounded can be given treatment priority and sent back.
If the wounded have any conditions that might endanger
their lives, such as asphyxia (stifl ing) and severe dyspnea,
shock, coma, severe vomiting and diarrhea, etc., they should
13 Combined Radiation–Burn Injury

347
be diagnosed quickly and given priority treatment. During
the explosion of a small nuclear weapon and near to the cen-
ter of the explosion, radiation sickness of affecting the brain
type may appear, and a corresponding combined radiation
injury. If the wounded appeared to have sustained vomiting,
even diarrhea, they may have a severe combined radiation
injury or severe radiation sickness.
13.8.1.3 Early Diagnosis in the Early
Treatment Station
After being saved from the infl icted area, the wounded have
to be sent to the early treatment station, where there are bet-
ter conditions than those in the infl icted area to obtain neces-
sary investigation and examination. To meet the demands of
treating large numbers of wounded and treating them by
grade within a short time, after the wounded have been
reached, early diagnosis should be made as soon as possible
so that the degree of severity can be differentiated in time,
and it can be decided which of the wounded should have
priority treatment and operation. The wounded contaminated
by radiation can then be separated to be cleaned and it can be
arranged for them to stay there for further treatment.
Early diagnosis can be made by the following aspects of
understanding and analysis:
1. The condition of the wounded during the time of the
explosion
Carefully understanding the position of the wounded
at the nuclear explosion, to know whether there is a hid-
ing place for protection, or whether the wounded can see
the scene of explosion or hear the sound the of explosion,
to know how long they are staying in the infl icted area,
especially how long they are staying and working in the
seriously contaminated area, and how they leave the
infl icted area. These conditions are helpful in indirectly
inferring the possible injury that has occurred.
2. The circumferential environment of the wounded
Understanding the situation that has been destroyed in
which the wounded had been at that time will be condu-
cive to judging the injury that has occurred.
3. To infer from the burn condition
The severity degrees of injuries caused respectively by
the three instantaneous infl icting factors had mutual con-
nections. When having found the regularity, and from the
burn conditions, which are easier to diagnose, we could
indirectly infer the possible radiation injury and visceral
injury that occurred. During the nuclear explosion of
small weapon, there were no distinct differences between
the extent of injury induced by the three instantaneous
infl icting factors. By increasing the equivalent areas pro-
ducing the burn injury were larger than those with a blast
injury and a radiation injury. Therefore, to the exposed
subjects, when the small nuclear weapon was explored,
and a certain degree of burn injury was found, we would
consider that the same degree or a more serious degree of
blast injury and radiation injury could occur, the less the
explosive equivalent was, the more severe the combined
radiation injury would be. When the medium nuclear
weapon was explored, the burn degree and the blast injury
were approximately the same, or the burn injury was a
little more severe; a burn injury more severe than a
medium degree injury may be combined with radiation
injury. When a large nuclear weapon was explored, the
degree of burn would be more severe by one or two
degrees than the blast injury. Certainly, to indirectly infer
a blast injury and radiation injury from the degree of burn
was for reference only, we had to judge them comprehen-
sively in the light of other aspects. When the wounded
were under protective and concealed conditions, as most
of the burns were fi re burns, and the conditions were more
complicated, we were unable to infer other injuries using
the above methods.
4. Judging by the early symptoms
In a combined injury, the combined burn of the body
surface and the trauma are easily diagnosed; thus, the key
point of diagnosis is still the combined radiation injury
and visceral injury. Early diagnosis of all kinds of com-
bined injuries should be mainly based on the early symp-
toms and signs, and all the characteristics mentioned
above for reference, to comprehensively judge the injury
conditions. If the subject has a large area of burn injury
and no distinct early symptoms of radiation sickness, they
may have a combined injury with a burn as the main con-
dition; if the subject has nausea, vomiting, and diarrhea,
simultaneously with symptoms of burn and blast injury,
they may have a combined radiation–burn blast injury. If
the subject after injury had a severe wound condition,
which was not in accordance with burn injury of the body
surface and the condition of trauma, they should be con-
sidered to have a radiation–burn or visceral blast injury; if
the local burn area appeared to have the characteristics of
a combined radiation injury, a combined radiation injury
above the medium degree should be considered.
13.8.1.4 Determining the Diagnosis
The medical reserve units in the rear should examine the
subjects from all sides and decide the diagnosis on the basis
of a classifi ed diagnosis and active treatment performed at
the infl icted area and by the organization involved in early
treatment. The history, symptoms, signs, and blood pictures
should be understood, and the irradiated doses examined. If
the conditions permit, X-rays, ECG, supersonics, isotopic
scanning, and blood biochemical examination should also
be examined, the conditions analyzed comprehensively, and
a defi nite diagnosis of the kind of the wound made, and
fi nally there should be an effi cient and prompt treatment for
the wound.
13.8 Diagnosis and Comprehensive Treatment for Radiation–Burn

348
The diagnostic meanings of several examination targets in
combined injury are briefl y discussed in the following:
1. Examining the blood picture
During burn injury, blast injury, and radiation sick-
ness, the number of WBCs in the peripheral blood and
their differential counts had different extents of changes
and characters. In combined injury, as the type of wound
and the wound condition were different, the changes were
more severe, and each had its defi nite characteristics. To
grasp these characteristics would have a certain value in
distinguishing different kinds of combined injury and
judging the wound conditions. For example, burn–blast,
burn–radiation blast, and radiation burn–blast combined
injuries are three common kinds of combined injuries.
They all had burn and blast injuries from the examination
as a trauma, while the changes in their blood pictures
showed different trends. The general trends of the changes
in the total count of WBCs were that it increased in com-
bined burn–blast injury, it fl uctuated or decreased a little
in combined burn–radiation blast injury, while in radia-
tion burn–blast combined injury it decreased. The changes
in the percentages of neutrophil granulocytes were that
they increased in combined burn–blast injury, they
increased or fl uctuated in combined burn–radiation blast
injury, and decreased or fl uctuated in the combined radia-
tion burn–blast injury. The changes in the lymphocyte
count were that it increased or decreased a little in com-
bined burn–blast injury, while in burn–radiation blast and
radiation combined burn–blast they all decreased.
In general, it was considered that there was a close
relationship between the change in the number of WBCs
at the early stage of radiation–burn and the degree of
severity of wound conditions; therefore, the reductive
degree of the total count of WBCs and the number of
lymphocytes may be used as a reference for distinguish-
ing among the different wound conditions.
2. Examining the irradiation doses
To decide whether the subjects suffered from com-
bined radiation injury and its degree of severity in addi-
tion to understanding and examining them according to
all kinds of methods as mentioned above, we had to know
the exact doses of nuclear irradiation to which the sub-
jects were subjected if they wore a personal radiation
dosimeter. Meanwhile, this would to a certain extent rep-
resent the strength of nuclear irradiation within that dis-
tance and condition, which would have reference value
for diagnosing the subjects under a similar condition.
As for the subjects sent back away from the irradiated,
contaminated area, every grade of medical treating orga-
nization should examine them for radioactive contamina-
tion and classify them by using the radiological
examination artifi ce that had been equipped. To fi nd out
whether the burn had been contaminated by radionuclide,
the wound should be examined for radioactive contamina-
tion, and the contaminated scope and extent should be
known. The diagnosis combined with the conditions of
the subjects and injury should be decided, so as to treat
them promptly.
Using β, γ detector can easily examine the radioactive
contamination for the burn area. Before detection, the
wound should be cleaned using cotton or gauze absorbing
2–3 % citric acid or clear water from the centre to the
peripheral skin, paying attention to preventing the radio-
nuclide falling onto the wound, and the cotton or gauze
should be examined for radioactive dose, to decide whether
the skin is clean. Then, the burn area should be examined
for dose, to decide the radioactivity of the secretion from
the burn wound, samples should be collected from the
burn wound by using sterile fi lter paper, cotton, gauze or
pipette, and the dose measured. This examination should
be carried out within 8 h after injury because the radioac-
tivity of the burn area will be relatively reduced after a
long time has passed, which is due to the absorption and
disintegration of the radionuclides; thus, the results of the
examination are not enough to show the practical level of
the early contamination of the burn tissue.
During examination of the radioactive contamination
of the burn area, the differential diagnosis from the radio-
activity in vivo (induced, absorbed) should be made. After
determining the burn area contaminated with radionu-
clide, the absorbent extent of radionuclide and the treating
effect should also be determined exactly, for which the
removed tissue from the burn wound, used gauze, cotton,
and instruments from the operation, and the collecting
lavage fl uid should be measured for radioactivity, then
analyzed and compared with the original results. If neces-
sary, samples of blood, urine, and stool or directly on the
thyroid area should be collected to determine the radioac-
tivity, and to understand the extent of absorbance so as to
treat them promptly.
13.8.2 Comprehensive Measures
for Treatment
13.8.2.1 Principles of Comprehensive Treatment
1. The subjects with radiation–burn from nuclear explosion
should have graded treatment. In general, treatment is
divided into three grades: saving in the infl icted area,
treatment at an early stage, and followed treatment.
2. The principles and experiences of treating burn and
wounds in peacetime and conventional war are fully
similazied; the treatment principles and experience in all
kinds of single injuries are fully used, and the subjects
are treated according to the characteristics of
radiation–burn.
13 Combined Radiation–Burn Injury

349
3. Emphasis is placed on treating the main wound in a radia-
tion–burn. It should be distinguished whether the main
wound is a radiation injury or a burn injury, while the
secondary injury is not to be neglected.
4. Attention should be paid not only to the general treat-
ment, but also to appropriately treating the local wound,
to make the two sides complement each other.
5. The contradiction existing in the two injuries during treat-
ment should be properly dealt with. Attention should be
paid to the developing period of the course, and particular
emphasis should be placed on the treatment at different
stages.
13.8.2.2 Contents and Steps for Comprehensive
Treatment
1. Contents of comprehensive treatment
(a) Treat early, including anti-shock and visceral protec-
tion, especially protecting the heart function
(b) Treat the burn wound at an early stage, work hard as
soon as possible to make the combined injury become
a single radiation injury
(c) Study and compile the anti-radiation drugs concerned
and the hematopoietic factors, and determine the
method used and the practical effects
(d) Adjust the immunity of the intestinal tract to prevent
and treat enterogenous infection
(e) Anti-infection, using antibiotics if there are indications
(f) Transfuse “treated blood,” which contains only a few
lymphocytes.
2. Steps of graded treatment
(a) Saving the subjects in the infl icted area
(b) Early treatment
(c) Treatment in the medical reserve units in the rear:
mainly including anti-shock, prevention of infection,
treatment of hemorrhage and hematopoietic dysfunc-
tion, to deal with the burn wound, etc.
13.8.2.3 Treatment of Radiation–Burn
Mainly with Radiation Injury
As for the radiation–burn mainly with radiation injury, the
fi rst comprehensive treatment measures adopted according
to different wounds and different stages.
1. First aid including extinguishing a fi re, covering the
wound surface; keeping calm, relieving pain, keeping
warm, taking burn drinks orally (containing salt 0.3 mg,
sodium bicarbonate 0.15 mg and the right amount of
glucose in each 100 ml of water) to prevent shock; tak-
ing compound sulfamethoxazole (SMZco) to prevent
infection; preventing and treating suffocation.
2. Intravenous infusion of 500 ml of low molecular dextran
to treat symptomatically and supplement nutrition.
Meanwhile, antitoxin is injected for prevention of
tetanus.
3. Using drugs to prevent irradiation at the early stage. The
drugs that are effective for acute radiation sickness also
have effects on radiation–burn, for example, 1 day after
injury use anti-radiation drugs, which have a treatment
effect as early as possible, such as E838, 500, 523, 408,
etc., and use drugs that can increase WBCs as early as
possible, such as cepharathine, tremella polysaccharide,
mushroom polysaccharide, etc. If the condition permits,
the treatment effect of using WR2721 for prevention,
which is compatible with E838, is better. When suspect-
ing subjects of having radioactive substance in their
body, 100 mg of potassium iodide should be taken orally
as soon as possible; if necessary, measures needed to
speed up excretion may be adopted.
4. Protecting hematopoietic function, preventing hemor-
rhage, correcting dysfunction of the microcirculation,
and the disorder of the water and electrolyte balance.
5. After using compound sulfamethoxazole (SMZco) or
penicillin to prevent infection at an early stage of injury,
if the subject has fever and the temperature does not
decrease or the total count of WBCs is reduced to
2.0 × 10 9 /L, streptomycin or gentamicin should be used
as a supplement. If using the above drugs for 3 days
while the infection was still not controlled, the large
dose combined with broad-spectrum antibiotics should
be used, and attention should be paid to the prevention
of fungal infection.
6. If the total count of WBCs in the peripheral blood
decreased to 1.0 × 10 9 /L, the suspension of WBCs may
be infused; if the platelets decreased to 20 × 10 9 /L or
severe hemorrhage occurred, the suspension of platelets
may be infused. If transfusion of fresh whole blood is
needed, it is better to irradiate it with 15–25 Gy by γ-rays
for treatment in advance before transfusion, which could
reduce the rejective reaction.
7. As for the subjects who suffered above middle degree
burns, the measures of disinfection and separation
should be strictly controlled. Use clean laminar fl ow
according to the needs and possibility. However, in the
subjects with severe radiation–burn, the irradiation
doses are above 8 Gy; it may be considered to transplant
hematopoietic stem cells of peripheral blood with non-
myeloblastic allo-gene from donors who match for
human leukocyte antigen (HLA) and attention paid to
the prevention of graft-versus-host disease (GVHD). As
for the subjects with chest irradiation, the prevention of
interstitial pneumonia should have much attention
devoted to it at the later stage.
8. Treatment for the burn wound
(a) Debridement at early stage, using normal saline and
0.1 % benzalkonium bromide solution to clean the
wound surface. If the wound had been contaminated
with radionuclide, removal of the contamination
13.8 Diagnosis and Comprehensive Treatment for Radiation–Burn

350
should be carried out as soon as possible, and can be
done with debridement at the early stage.
(b) Apply
preparations
with
bactericidal,
anti-
phlogistic, astringent, and promoting healing effects
on second-degree burn wounds, maybe also use cel-
lular factors to prevent wound infection.
(c) With regard to the third-degree burn wound,
removal of the eschar and autograft should be car-
ried out as early as possible, striving for the wound
to heal before the critical stage and turn the com-
bined injury into a single injury, but a concrete
arrangement should be considered comprehensively
according to the general condition. If the burn sur-
face is less than 10 % of the TBSA and the sub-
jects’ conditions are good, removal of the eschar
and autograft at the early stage should be adopted. If
the burn surface is large and the subjects could bear
the operation of cutting the eschar and allograft or
transplanting an allograft alternating with autograft
to cover the wound and take them through the criti-
cal stages and then autografting again. If the general
condition of the subjects is severely not suitable for
operation, the eschar should be strictly retained, and
the general treatment simultaneously strengthened
to prevent infection of the wound (particularly the
pyemia of the wound), until entering the restoring
stage with the eschar falling off or being removed
followed by autografting.
(d) When taking the skin and skin grafting, local anes-
thesia may be chosen or combined intravenous
anesthesia with ketamine.
9. When the subjects have a burn of the respiratory tract,
the oral cavity should be cleaned; if the subjects have
edema of the throat, which can cause asphyxia, a trache-
otomy should be performed promptly; if there are
spasms of the bronchi, agents for bronchiectasis should
be given, oxygen should be inhaled, and the respiratory
tract kept wet.
10. When the subjects had a burn of the retina, measures for
promoting edema absorbance, infection control, and
scar formation reduction should be adopted.
Second, the subjects with radiation–burn, who had been
considered to be clinically healing after treatment, should be
followed strictly and examined regularly for their health.
Attention should be paid to the possibility of developing scar
contraction, or even a deformity, the long-term effects, and if
any, the corresponding treatment should be given. According
to the condition of restoration, the subjects may convalesce,
rest or have suitable work arranged for them. If they become
disabled during public service, they should enjoy the treat-
ment stipulated by the nation.
13.8.2.4 Treatment for Burns Contaminated
by Radioactive Substances
1. In general, except for treating severe shock or other emer-
gency, as for a contaminated burn; removal of the con-
taminator must be carried out as early as possible, to
remove the contaminant from the burn wound to the
greatest extent.
2. Washing away the contaminant 1 h after contamination may
remove 70 % of the radioactive substance from the burn
area. If washing 2 h after contamination only 10 % of the
radioactive substance can be removed. If washing much
later, only 3–5 % of the contaminant can be removed. If
treating the wound by carrying out a surgical operation 2 h
after contamination, 30–70 % of the radioactive substance
may be removed. If more than 6 h after contamination have
passed, it is not easy for either surgical operation or another
removal method to have effi cacy under ordinary conditions.
3. The concrete methods for removing the contaminant from
burn wounds are:
(a) Cover the wound at fi rst, then wash the skin around
the wound with 2–3 % soapsuds and clear water.
After the wound has dried, apply the aseptic skin
preparation using tincture iodine and alcohol as
before the routine operation was carried out. Do not
use anything that promotes dissolving and absorbing
of the radioactive substance (such as gasoline or ethyl
ether) to clean the skin. Do not shave the skin hairs to
avoid injuring the skin and increasing the chance of a
radioactive substance entering into the body.
(b) Rinse the wound surface with 2–3 % soapsuds, nor-
mal saline or ethylenediamine-tetraacetic acid solu-
tion, simultaneously using gauze or cotton to clean
the wound gently to remove the radioactive substance
and other foreign bodies contaminating the wound.
(c) Dry the wound, and examine the contaminating con-
dition. If the radioactive contaminant is not removed,
wash and clean the wound repeatedly.
(d) After the wound has been washed and cleaned, the
radioactive substance may be removed. The radioac-
tive substance on the wound surface is mainly
removed by the mechanical action of washing and
cleaning; thus, the amount of solution for washing
should be appropriate, must not be too much, and its
fl ow speed should not be too rapid.
(e) If the wound is deep enough, the contaminants are
diffi cult to remove fully when simply using washing
and cleaning; thus, after washing the fi rst stage of the
operation should be immediately carried out.
During operation the principles of surgical
enlargement of the wound should be followed
strictly, removing all the contaminated necrotic
13 Combined Radiation–Burn Injury

351
tissues, clearing the wound and clearing away for-
eign bodies, then examining for contamination once
more. In general, after carrying out a thorough
removal operation, most of the radioactive sub-
stances should be removed.
After enlarging the wound, wash it with normal
saline again until satisfi ed or until the radioactive
substance cannot be further reduced at the wound. If
the amount of the radioactive substance in the wound
was below the permitted level, the wound would be
sutured, to aid primary healing.
If the amount of the radioactive substance in the
wound is still higher than the permitted level, the
wound should be loosely fi lled with saline gauze,
which is helpful for drainage and getting rid of
remaining radioactive substance from the wound.
4. When carrying out the contaminated operation of the
radioactive substance, the operation table should be
specially pointed or the table should be covered with a
plastic cloth.
(a) After operation the operating instruments used should
be washed and scrubbed with soapsuds and hot water
to remove the contaminants.
(b) Instruments that are severely contaminated should
first be washed with 0.5–1 % citrate or hydrochlo-
ric acid solution, then rinsed with running
water, and finally re-examined for radioactive
contaminants.
(c) The waste water, contaminated tissues that have been
removed, and other polluted items after washing
should be collected in hermetically sealed dust bins,
then buried deep in a pointed place.
The treatment principles and measures mentioned above
are suitable for the treatment of radiation–burn from nuclear
explosion They also provide treatment for a medical emer-
gency caused by severe nuclear accidents.
Translator: Ciai Zhang
13.8 Diagnosis and Comprehensive Treatment for Radiation–Burn

353
Z. Yang, Chinese Burn Surgery, DOI 10.1007/978-94-017-8575-4_14,
© Springer Science+Business Media Dordrecht and People’s Medical Publishing House 2015
Multiple-organ dysfunction syndrome (MODS), known as
sequential system failure in the early years, had been initially
described by Tilney et al. [ 1 ] in 1973. With improvement in
recognition, the concept of MODS has been revised unceas-
ingly. It has been known as progressive sequential multiple
organ failure [ 2 ], multiple organ failure [ 3 ], multiple system
organ failure, MSOF [ 4 ]. In 1991, a conference of the
American College of Chest Physicians/Society for the
Critical Care Medicine (ACCP/SCCM) termed this syn-
drome multiple organ dysfunction syndrome, MODS, which
has been employed until now [ 5 ]. In China, t the national
conference on critical care medicine held in October 1995,
the concept of MODS was determined to replace
MSOF. MODS are defi ned as a clinical syndrome, sequential
dysfunction of more than two separate systems or organs
within 24 h caused by various factors, both infective and
non-infective (trauma, burns, pancreatitis, etc.) [ 6 ].
The concept of MODS was fi rst introduced into the
domain of burn surgery in the 1970s by Chinese scholars.
Although China had had many exclusive achievements in the
treatment of burns that had saved the lives of countless burns
patients, with a leading position all over the world, many
critical patients had passed away because of subsequent mul-
tiple organ failure, which had perplexed many clinicians.
With the introduction of MODS, scholars have recognized
this new complication in a brand new way. However, the
study of MODS was just beginning, the manifestation and
pathogenesis were still to be recognized, early diagnostic
indications, laboratory markers, and a standard animal model
of MODS were lacking, let alone an effective treatment.
With the guidance of Dr. Sheng Zhi-yong, some of the
famous burn units had cooperated to tackle this problem. The
studies began in 1980s, were designated as a key military
program in 1987, and consequently received more than 20
supportive grants. The studies have covered every compo-
nent from the pathogenesis to the therapeutics of MODS. With
great efforts across two decades, the pathogenesis and patho-
physiology of MODS caused by burn has been revealed
gradually, the diagnosis criteria concerned have been revised,
and a set of effective interventions of treatment and preven-
tion has been established. Some achievements are interna-
tional patents, which have been largely devoted to the
development of MODS theories. With the application
achievements in clinical practice, the incidence and the mor-
tality of MODS caused by burns have been reduced to a large
extent, and the level of diagnosis and therapeutics have been
greatly elevated. In general, the achievements are discussed
as follows.
14.1
Predisposed Causes and Clinical
Features of MODS
Multiple organ dysfunction syndrome caused by large-area
burns was fi rst reported by the 1st Hospital Affi liated to the
PLA General Hospital in 1983 [ 7 ]. Among 108 patients with
a burn area covering more than 50 %, the patients with more
than 20 % third-degree burn were admitted to the hospital
during 1970–1980, of whom 20 developed MODS, nine
cases were related to shock during the early stages, and
another six patients were related to severe infections. The
results indicated that besides burn itself, shock and infection
are important causes of MODS. After that, various retrospec-
tive studies revealed that multiple factors, such as blood
transfusion, skin grafting, defi ciency of calories, and iatro-
genic factors, could induce MODS in patients with burn
injury [ 5 ]. Studies from other burn units also revealed similar
conclusions [ 8 – 10 ].
According to clinical data, the procedure of MODS could
be classifi ed into two types:
1. Monophase-velogenic: within 24 h after the onset of pro-
topathy, two or more systems develop dysfunction simul-
taneously. In this type, the primary disease usually proves
to be very severe, but those cases in which the patient died
of organ failure within 24 h are generally attributed to
failure of resuscitation, rather than MODS.
Postburn Multiple Organ Dysfunction
Jiake Chai and Zhiyong Sheng
14

354
2. Diphase-tardive: in this type, after the onset of dysfunc-
tion of one important system or organ, usually circulatory,
renal or respiratory system, a stable period is maintained,
and consequently more organ failure occurs. This type
has proved to be more common, and the common mani-
festation includes fi ve aspects:
(a) Presence of shock and infection before the onset of
MODS. The more severe the shock is, the more
severe the infection is that occurs, the higher the inci-
dence and mortality of MODS.
(b) Over-infl ammatory responses: refl ected by changes
in body temperature, respiratory rate, heart rate,
WBC count, and neutrophils.
(c) Metabolism disorder: this includes elevated oxy-
gen consumption, a basic metabolic rate, and an
abnormal metabolic path, i.e., great consumption
of protein and limited employment of glucose, an
important energy substrate, and marked autophagy,
which could not be rectifi ed by exogenous nutri-
tion supplement.
(d) Hyperkinetic circulation, so-called elevated CO with
reduced peripheral vessel resistance.
(e) Organ failure [ 5 ]: a different sequence has been
reported. In general, the sequence proves to be respi-
ratory, renal, GI tract, coagulation, hepatic, and circu-
latory. The sequence could be infl uenced by factors
such as aspiration injury, delayed resuscitation, and
complications. With aspiration injury, initial onset
organ is usually the lung, the renal system usually
fails when resuscitation is delayed, and the injured
organ fails early when trauma is the primary cause
[ 8 – 12 ].
In MODS, the injury of organs is reversible, leaving lit-
tle trace once cured, and seldom becomes chronic organ
dysfunction.
14.2
Establishment of the MODS Model
Establishment of an ideal animal model, which is an impor-
tant basis in the study of pathogenesis and therapeutics of
MODS, remains a diffi cult problem in the world. There are
problems in the previous models, i.e., a single causative fac-
tor, the short survival time, inadequate diagnostic criteria,
lack of organ support, and as a result, these models could
not imitate actual clinical conditions. With great efforts for
8 years, raising key factors, criteria, the organ dysfunction
scoring system in an animal model, the scholars at the 1st
affi liated hospital of the PLA General Hospital fi rst success-
fully duplicated the biphase-tardive MODS model in ani-
mals, both monophase-velogenic and biphase-tardive types
were included, the causative interventions covered common
factors such as shock and infection [ 13 – 16 ]. The achieve-
ments have provided marked advantages to scholars all over
the world.
14.3
Pathogenesis of MODS
With regard to the pathogenesis of post-burn MODS, both
domestic and foreign scholars have carried out a great deal of
research over the past two decades, and have put forward
some valuable perspectives. Scholars in China concentrated
their work mainly on the following aspects.
14.3.1 Ischemia–Reperfusion and Organ Injury
According to clinical studies, ischemia, anoxia caused by
hypovolemic shock after severe burn, and reperfusion accom-
panied by fl uid resuscitation could lead to various injuries of
the major organs, or even severe dysfunction. Besides isch-
emia and anoxia, two other mechanisms are involved.
14.3.1.1 Oxygen Radical Injury
Oxygen radical injury is related to the reperfusion of isch-
emic tissue. The energy store of tissue and cells is largely
consumed in ischemia. ATP, as the major energy carrier, is
thoroughly degenerated and mass hypoxanthine is produced.
With the recovery of tissue perfusion, hypoxanthine, with
catalysis of xanthine oxidase, uric acid is produced, and a
large amount of oxygen radicals are produced simultane-
ously, which causes various oxidative damage of tissue and
cells through its special chain reaction. In the limited condi-
tions, the early studies on reperfusion and oxygen radical
injuries, mainly observed the relationship between organ
dysfunction and MDA, a product of the oxygen radical reac-
tion [ 17 , 18 ]. Through MRI, Yang et al. [ 19 , 20 ] have detected
mass oxygen radicals in the blood and tissues of animals
with a large-area burn but delayed resuscitation, which pro-
vided direct evidence of oxygen radical injury.
14.3.1.2 Apoptosis
Apoptosis, known as programmed cell death, is a type of cell
death that is different from cell necrosis. Apoptosis is com-
pleted through the concentration and coagulation of cell
plasma and consequently phagocytized by macrophages,
without overfl ow of cellular content or eruption of the cellu-
lar membrane. As a result, no infl ammation occurs. Apoptosis
is a key physiological course for embryogenesis and mainte-
nance of cell balance in the organs. It has been indicated by
recent studies that ischemia and reperfusion caused by
delayed resuscitation after severe burns could accelerate the
apoptosis of endothelial cells and parenchymal cells, and
organ dysfunction could get aggregated [ 21 – 23 ].
14.3.2 Bacterial Toxin and Systemic
Infl ammatory Response
Acute infl ammatory response is one feature of MODS. Mass
necrotic tissues and various organ injuries caused by isch-
14 Postburn Multiple Organ Dysfunction

355
emia and reperfusion after severe burn can induce a systemic
infl ammatory response. In recent years, scholars have paid
more attention to the systemic infl ammatory response
induced by toxins from bacteria. In the early stages of a burn
the toxins of bacteria, proven to be endotoxins, mainly come
from the intestinal tract. Current studies reveal that ischemia
and reperfusion of the intestinal tract, and oxygen radical
injury can destroy the mechanical and immunological barrier
of the mucous membrane, and the micro-ecological balance
simultaneously, which leads to translocation of bacteria and
endotoxins in the intestinal tract [ 24 – 27 ]. In the advanced
stages, the toxins mainly come from the focus of infection,
which differs according to the type of bacteria, and includes
both exotoxins and endotoxins. Endotoxins have been stud-
ied suffi ciently among mechanisms of infl ammatory
responses induced by bacteria toxins. Endotoxin combines
with free lipopolysaccharide binding proteins (LBP), which
transfer endotoxins to the lipopolysaccharide receptor CD14
on the membrane of macrophages, through a series of signal
transductions, cells become activated, infl ammatory factors
are secreted, and infl ammatory responses are induced.
According to current opinions, the pathway of endotoxin-
activating macrophages to release infl ammatory factors has
been proved to be the major pathway. Besides, CD14,
CD11b, CD18, and Toll-like receptor on the membrane of
macrophages also play the role of endotoxin receptors. The
functions of these receptors are different, and the detailed
signal transduction pathway and effects have not yet been
revealed.
According to a study by Yao et al. MAPK, Janus kinase
signal transduction, JAK/STAT, and NF-κB are related to the
activation of receptors [ 28 ]. It was observed in vitro that
endotoxins could activate the former pathway in infl amma-
tory cells, playing an important role in the regulation of cell
physiological and pathological reactions. We have recog-
nized that the pathway of MAPK participates in the activa-
tion of various cells in MODS. The signifi cant role played by
the p38 MAPK pathway in inducing an MPS reaction and
iNOS expression has been emphasized. The regulatory role
of the MAPK pathway on infl ammatory and anti-
infl ammatory responses and the cross talk among other path-
ways are also further discussed. Meanwhile, the JAK/STAT
pathway is closely related to acute tissue damage and the
onset of shock in MODS [ 29 ]. Exotoxins have been paid
close attention, especially Staphylococcus aureus entero-
toxin B (SEB), which features super-antigen, and its special
meaning in toxic shock syndrome have attracted lots of
scholars. In the model of rats with sepsis and staphylococcus
attack after severe burns, SEB is found in major organs such
as the heart, lung, kidney, and liver, is related to organ dys-
function and the disorder of balance between infl ammatory
and anti-infl ammatory responses in local tissue [ 30 ]. Among
the major organs, the liver and kidney enjoy the highest con-
centration of SEB, indicating that liver and kidney may play
an important role in the accumulation and elimination of
SEB. The monoclonal antibody of SEB, neutralizing its tox-
icity, represses the progression of infl ammation caused by
Staphylococcus aureus ; as a result, organ dysfunction can be
improved [ 31 ].
Among infl ammatory factors released by macrophages,
the effects of TNFα, IL-1, and IL-6 are outstanding. These
factors could activate neutrophils, endothelial cells, lymph
cells, and platelets, to release chemical mediators or bioac-
tive substances, such as lysomal enzyme, elastase, MPO,
collagenase, oxygen radicals, lipid mediators, PLA2, pep-
tides, and cytokines such as TNFα, IL-1, IL-6, PAF, CSF, etc.
Lysomal enzyme, elastase, MPO, collagenase, oxygen radi-
cals are produced by neutrophils, their direct bio-toxicity can
help attack and destroy target substances such as invading
microbials and necrotic tissues; others without bio-toxicity
could also infl uence functions of organs or systems, such as
the circulatory, respiratory, metabolic, coagulation, and tem-
perature regulating systems, and the immune system to regu-
late endocrines with feedback.
As was generally accepted before, infl ammatory factors
in the early stage (TNF-α, IL-1) are key mediators in decom-
pensatory infl ammatory responses and tissue injury, but cur-
rent studies reveal that high mobility group box-1 protein,
HMGB1, as advanced-stage infl ammatory factors, may par-
ticipate in the pathogenesis of MODS [ 32 ]. The so-called
advanced stage infl ammatory factors refer to those observed
after TNF-α and IL-1 within 6 h after burns, i.e., HMGB1,
which lasts longer. HMGB1 is a series of low molecular
weight nucleoproteins, rich in electric charge. HMGB-1 and
HMGB-2 are the richest, which are expressed both intracel-
lularly and extracellularly. In nucleus, HMGB1 correlates
with lots of biological courses, such as the duplication of
DNA, and the differentiation of cells and gene expressions.
After being secreted outside the cells, HMGB1 may mediate
the pathogenesis of sepsis and MODS, as a new infl amma-
tory factor. As indicated in animal experiments, the expres-
sion of the HMGB-1 gene is markedly elevated in the liver,
lung, and intestine of animals 6–24 h after severe burn and
abdominal infection, and lasts until 72 h after the burn; focal
HMGB1 over-expression is closely related to organ dysfunc-
tion induced by endotoxins [ 33 ]. Similarly, in sepsis induced
by Staphylococcus aureus infection, expression of HMGB1
mRNA is markedly elevated in major tissue. This dynamic
feature is obviously different from those of early-stage cyto-
kines such as TNF-α and IL-1β; the elevation of HMGB1
gene expression occurs later and lasts longer [ 34 ]. Some data
reveal that intraperitoneal administration of purifi ed recom-
binant HMGB1 can lead to manifestations of sepsis, while a
larger amount can cause death in mice. Generally speaking,
HMGB1 itself could induce a series of pathophysiological
effects, even death. According to clinical observation, serum
HMGB1 is markedly elevated in severe burns and sepsis,
related closely to the onset and progression of sepsis [ 35 ]. As
indicated in further study, the therapy of N-butyric acid, an
inhibitor of HMGB1, can effectively reduce the expression
14.1 Predisposed Causes and Clinical Features of MODS

356
of HMGB1 mRNA in liver, lung, kidney, and heart, conse-
quently improving organ function and infl ammation as well.
What is more, N-butyric acid administration can reduce the
mortality of d1 ~ 6 in septic animals, whose prognosis is
markedly ameliorated [ 36 ]. As a result, N-butyric acid treat-
ment in the early stages of sepsis can help to reduce the over-
expression of infl ammatory factors such as HMGB1, and
ameliorate the survival rate of animals. These results indicate
that interventions toward the advanced-stage cytokine,
HMGB1, may improve the therapy for sepsis and MODS.
According to clinical observations, bacteria toxins can be
detected in the serum of severe burn patients with delayed
resuscitation. At the same time, infl ammatory factors of both
the early stage and the advanced stage are elevated, which
have confi rmed the importance of bacterial toxins in infl am-
matory responses.
14.3.3 Mechanism of Systemic Infl ammation
Reaction Losing Control
Among the patients who suffer from the systemic infl amma-
tory response, a few of them experience loss of control.
Then, what reason on earth drives them to lose control of
infl ammation, consequently leading to MODS? The question
still remains unknown. Some scholars have raised some
hypotheses and viewpoints, four of them prove to be the
most meaningful, one was raised by a Chinese scholar, the
other three have been confi rmed by our scholars in the burns
fi eld.
14.3.3.1 Hypothesis of Diphasic Preexcitation
The hypothesis raised by Dr. Sheng Zhiyong and Dr. Hu Sen
has been confi rmed in animal models and in clinical practice.
In this hypothesis, MODS caused by trauma or burns experi-
ences two attacks or stress processes, known as ischemia–
reperfusion and infection. The initial attack plays a
preexcitation role, the second attack leads to infl ammation
and MODS. Diphasic preexcitation hypothesis is a compre-
hension of a hypothesis of ischemia–reperfusion and double
attacks, and clarifi es the essence of preexcitation in MODS
and the signifi cance of early diagnosis and intervention after
the initial attack [ 37 ].
14.3.3.2 Compensatory Anti-infl ammatory
Response Syndrome Hypothesis
Compensatory anti-infl ammatory response syndrome
(CARS) is also called “immune paralysis” or “window of
immunodefi ciency”, etc. It was raised by Bone in 1996,
against a background in which anti-infl ammatory therapy
encountered frequent failures [ 38 ]. In the CARS hypothe-
sis, infl ammatory factors and anti-infl ammatory factors
share the same signifi cance in determining the prognosis
of infl ammatory responses. If the foreign attack is severe,
the release of infl ammatory factors loses control, then sys-
temic infl ammatory response syndrome (SIRS) or immune
accentuation appears, consequently leading to various
injury due to constant infl ammation. On the other hand, if
the reactions are too severe, a compensatory anti-infl am-
matory response occurs, the organism presents low
responses toward foreign attacks, with a manifestation of
hypoimmunity, or immune paralysis. Simple CARS are
seldom; what we usually see are both constant infl amma-
tion and hypoimmunity, i.e., both SIRS and CARS simul-
taneously, known as the mixed anti- infl ammatory response
syndrome, MARS. Recent study confi rms that the expres-
sion rate of HLA-DR in CD14 + monocytes is an important
indicator of immunity in an infl ammatory state. We have
observed in a multiple-center clinical trial that with eleva-
tion of TNF-α level in septic patients, expression of
HLA-DR is reduced, providing evidence for this hypothe-
sis [ 39 ].
14.3.3.3 Gene polymorphism Hypothesis
In clinical practice, not all severe burn patients suffer from
sepsis. We have reviewed 149 patients with severe burns
(burn area larger than 30 %), 57 of them (38.2 %) developed
sepsis, 97 patients (61.8 %) were free from sepsis, among
the septic patients, 10 (17.5 %) had MODS and six patients
died. The results indicate that some patients present affect-
ability by MODS and sepsis. Even among the patients with
similar conditions and therapies, some of them suffer from
sepsis and some do not. The prognosis of sepsis also differs,
some develop MODS, or even die, and some recover. The
reason why the prognosis differs from that of different indi-
viduals, and what substantial basis leads to this difference,
remains unknown. Scholars usually attribute this to the indi-
vidual differences. In severe infections and MODS, the term
of heterogeneity can help explain some diffi cult phenom-
ena, but only the factors such as age, primary disease, basic
status, onset time of therapy, and different therapies are
taken into consideration. Actually, features of genetics and
gene expression play signifi cant roles in determining het-
erogeneity. It has been confi rmed that the gene polymor-
phism exists in control gene expressions. Some scholars
have studied the polymorphism of the TNF gene in severe
sepsis after trauma; polymorphism sites exist in TNFα and
TNFα receptor type I (P55) and type II (P75), indicating the
signifi cance of the gene polymorphism in systemic
infl ammation.
Although detecting the gene polymorphism of the CD14
promoter, the expression level of HLA-DR in severe burn
patients, we investigated the correlation of gene polymor-
phism of CD14 with prognosis and HLA-DR expression of
severe burns patients. As is revealed in the results, among
71 cases, the sepsis incidence and mortality of patients of
14 Postburn Multiple Organ Dysfunction

357
genotype TT are higher than those of genotype TC and
CC. In the sepsis group, the level of antibody combined
with HLA-DR gradually reduces after the onset of a burn,
while it becomes elevated 5 days after the onset of burn in
the nonsepsis group. There is a signifi cant difference
between the two groups on days 3, 7, 14, 21, and 28. The
level of antibody combined with HLA-DR in the homozy-
gote of CC is markedly higher than that of the homozygote
TT on day 3, 14, and 21, but there is no signifi cant differ-
ence compared with the heterozygote TC. In the study, the
polymorphism of CD14-159C/T is closely correlated with
the affectability by sepsis. Among severe burns patients,
the homozygote of TT shows more affectability by sepsis,
with a more unfavorable prognosis. The level of HLA-DR
on the surface of their CD14 + monocytes is markedly lower
than that of the heterozygotes of TC and the homozygotes
of CC, indicating that the polymorphism of CD14-159C/T
could affect the immune paralysis of patients suffering
from severe burns [ 40 ].
Actually, the polymorphism of genes may be involved in
many links between the development of infl ammatory and
anti-infl ammatory factors. As the studies have progressed
further and further, we present a complete framework on
how gene polymorphism affects MODS.
14.3.3.4 Gut Hypothesis
As has been confi rmed in some foreign clinical trials, trau-
matic shock leads to persistent hypoperfusion in the intes-
tine. Even though suffi cient resuscitation is provided, some
patients still suffer from sepsis, eventually MODS and
death. As a result, persistent hypoperfusion in the intestine
can be considered an important initial factor in MODS. The
gut is not only the initial organ in uncontrolled infl amma-
tion, but also a target organ in MODS; this is the so-called
gut hypothesis in MODS. A series of studies from the team
of Dr. Sheng Zhi-yong have confi rmed that hypoperfusion
and reperfusion of the intestine could lead to remote organ
dysfunction. They have also duplicated the stable animal
model of MODS caused by intestinal ischemia–reperfusion
injury, which proved to be similar to the clinical status.
According to the current study, release of persistent infl am-
matory factors and delayed activation and apoptosis of cir-
culating neutrophils may play an important role in the
mechanism of how ischemia–reperfusion injury and uncon-
trolled infl ammation cause MODS. Furthermore, ischemia–
reperfusion injury in the intestine inducing apoptosis of
lymph cells in peripheral blood, and consequently, causing
immune disorder and sepsis, has been initially observed.
These results have intensifi ed our knowledge about the
mechanism of intestinal ischemia–reperfusion injury caus-
ing MODS, and have provided experimental agreement for
therapies of MODS induced by delayed resuscitation after a
severe burn [ 41 – 48 ].
14.3.3.5 Immune Dysfunction
More clinical and experimental data have confi rmed that
immune dysfunction is the key pathogenesis in MODS. On
the one hand, there is a strong infl ammatory reaction, and on
the other, there is suppression of the natural immune
function.
The ferocious attack on the organism leads to comple-
ment lysis, a large quantity of C5a is produced in the alterna-
tive pathway, consequently suppressing the bactericidal
function of neutrophils, and the affectability by pathogens is
elevated. At the onset of infection, some infl ammatory fac-
tors are produced and the apoptosis of neutrophils sup-
pressed. A large amount of neutrophils infi ltrating the tissues
did not develop apoptosis, but released intracellular oracles,
with several proteinase and free oxygen radicals produced.
Furthermore, the level of HMGB-1 rises to a peak, which in
turn increases the duration of the infl ammation.
The antigen HLA-DR is necessary in the process of anti-
gen presentation. The level of HLA-DR may show the func-
tion of two major antigen presentation cells, known as
monocytes and dendritic cells, and is markedly reduced in
burns patients. The more severe the burn, the greater the
reduction of HLA-DR. As a result, the reduction of HLA-DR
may last until 28 days after burn onset. Intraperitoneal admin-
istration of zymosan may duplicate sepsis and MODS. The
loss of dendritic cells is found in the animal’s spleen, and this
was also observed in patients who died of MODS.
In an experiment on ischemia–reperfusion of the intestine
in rabbits, apoptosis of the lymph cells in peripheral blood
could be observed, which leads us to imagine a similar phe-
nomenon in humans. In the spleens of patients who died of
sepsis and MODS, a larger amount of lymph cells was found
to be lost because of apoptosis. In macrophages, phagocy-
tized apoptosis bodies of lymph cells were observed. The
reason for the apoptosis of lymph cells may be the elevated
caspase-3 caused by various infl ammatory factors.
Meanwhile, elevation of HMGB-1 may lead to the drift of
Th1 to Th2, releasing IL-10, which may suppress the natural
immune function.
Generally speaking, fi erce infl ammation and the natural
immune mechanism coexist in the pathogenesis of sepsis and
so-called immune disturbance takes place. In multi-center
random control trials, anti-infl ammatory agent, ulinastatin,
and thymosinα1 received satisfactory curative effects, pro-
viding evidence for this pathogenesis.
14.3.3.6 Disorder of Coagulation
and Microcirculation
In the autopsy of patients who have died of MODS, micro-
thrombosis is observed in many small vessels, and a similar
phenomenon also exists in MODS animal models induced by
zymosan. It is caused by many factors. Infl ammatory factors
lead to the elevation of adherence factors, driving white
14.1 Predisposed Causes and Clinical Features of MODS

358
blood cells to adhere to the endothelium, which conse-
quently, releases tissue factors. Meanwhile, a reduction of
thrombomodulin and APC, which in return induces elevation
of the tissue factors, activates the coagulation procedure,
producing microthrombosis. On the other hand, elevation of
the prothrombin activator inhibitors cause the failure of
microthrombosis to be resolved. As a result, many micro-
thrombi obstruct the microcirculation. Furthermore, the
products of microbes induce the release of biopterin, activat-
ing iNOS, with a large amount of NO produced, the micro-
circulation becomes unstable. The fi nal consequence is a
severe disorder of nutrition uptake in tissue and cells, aggra-
vating direct damage to tissues, leading to MODS.
14.3.4 Effects of Systemic Infl ammatory
Reactions on the Organism
Systemic infl ammatory reactions could cause different forms
of damage and dysfunction of the organ through its fi nal
products, known as protease and oxygen radicals. As is
observed in the major organs of patients who have died of
MODS, a large amount of infl ammatory cell infi ltration
exists together with cell degeneration and necrosis, indicat-
ing the signifi cance of infl ammatory reactions in MODS
[ 48 ]. Other studies observed that systemic infl ammatory
reaction may aggravate organ dysfunction by inducing apop-
tosis [ 49 , 50 ]. In addition to the damaging effects on the
organ structure and function, uncontrolled infl ammatory
reactions also affect the functional activity of organs or sys-
tems, such as the circulatory, respiratory, metabolic, coagu-
latory, and temperature regulatory systems. The adverse
effects concerned include hypotension, disorder of oxygen
utilization, tissue edema, microthrombosis, hypercoagulabil-
ity, protein malnutrition, and metabolic disorder [ 51 ], among
which metabolic disorder and protein malnutrition in sepsis
have been most thoroughly studied.
In sepsis and MODS, hypermetabolism is present, with
the feature of autophagy and compulsivity [ 52 ]. The organ-
ism could become severely malnourished, the structure and
function of the tissue, organ, and various enzymes as well.
According to clinical practice, more than 90 % of patients
with severe infection suffering from persistent hypermetabo-
lism may develop MODS [ 53 ]. The studies concerned
include the following two aspects.
1. Glucose metabolism. Hypermetabolism with hyperlacta-
temia in sepsis has been proven to cause great damage to
the organism. Severe hyperlactatemia suppresses cardiac
contractility, cardiovascular and respiratory motorium,
aggravates hypoxia, consequently leading to elevation of
lactic acid. In return, a varied cycle is established. As has
been recognized by traditional opinions, the hyperlactate-
mia is caused by a disorder of the glucose aerobic metab-
olism following ischemia and hypoxia, i.e., so-called
aerobic oxidation and anaerobic glycolysis. According to
our studies:
(a) In sepsis caused by severe burn, even though suffi -
cient resuscitation ensures oxygen delivery and con-
sumption, marked glycolysis independent of reduced
tissue oxygen delivery still exists.
(b) In skeletal muscle in sepsis status incubated in vitro,
in spite of suffi cient oxygen supply, the level of lactic
acid produced is still elevated, indicating that aerobic
glycolysis exists in skeletal muscle after burn onset.
(c) The extent of aerobic glycolysis in skeletal muscle
also differs among different types of muscle, and is
much less in the soleus muscle (most red muscle)
than in the musculus extensor digitorum longus with
mostly white muscle.
(d) The basis of the studies above, as is confi rmed by our
study, ouabain, an inhibitor of Na + -K + -ATPase, mark-
edly suppresses the course of aerobic glycolysis.
Administration of monensin, a carrier of Na + , simu-
lates the enhancement of aerobic glycolysis, sharing
the same cytobiological mechanism with that in sep-
sis [ 54 – 56 ]. According to the studies above, enhance-
ment of Na + permeability in muscular cells and
elevation of the Na + level may activate Na + -K + -
ATPase, which is a signifi cant mechanism of aerobic
glycolysis in sepsis. Our study has corrected the tra-
ditional theory, and provides evidence for the treat-
ment of metabolic acidosis in sepsis.
2. Protein metabolism of skeletal muscle. We have been
investigating the pathophysiological mechanism of skel-
etal muscle protein hyperdegradation at the integral,
ex vivo, gene, and protein levels since 1997. As is indi-
cated in our study, levels of both tyrosine, which refl ects
total protein degradation, and 3-methylhistidine, refl ect-
ing desmin degradation, are enhanced in patients with
burns, sepsis or severe burns with sepsis. In particular the
degradation rate of desmin increases markedly. The more
severe the burn, the more obvious the degradation pre-
sented. In this process, ubiquitin of skeletal muscle is
clearly elevated in transcription and expression levels,
and the elevation of mRNA expression has a notable posi-
tive correlation with the elevation of Tyr and 3-MH. With
the degradation pathways of lysosome and calcium-
independent protein suppressed, the degradation rate of
the skeletal muscle protein is maintained. On the contrary,
it becomes markedly reduced if the ubiquitin–proteinase
degradation pathway is suppressed, which indicates that
hyperdegradation of skeletal muscle in sepsis is mediated
by the pathway of ubiquitin–proteinase, rather than lyso-
some or calcium-independent protein pathways. The
enhanced degradation is closely correlated with activa-
tion of ubiquitin–proteinase degradation at the transcrip-
tion level [ 57 – 60 ]. The study has provided accordance in
the regulation of hyperdegradation in sepsis. Further
14 Postburn Multiple Organ Dysfunction

359
study has confi rmed that disorder of the metabolic hor-
mones and infl ammatory factors is the key reason for
hyperdegradation [ 61 – 63 ].
14.4
Revised Diagnostic Criteria of MODS
The diagnostic criteria of SIRS and MODS were fi rst put
forward by American scholars, but the criteria are very sensi-
tive and nonspecifi c, encompassing the vast majority of
patients suffering from extensive thermal injury, which
weakens their value in clinical application. Under such con-
ditions, Chinese scholars revised the initial criteria [ 64 ].
14.4.1 Diagnostic Criteria of SIRS and Sepsis
In 1991, the ACCP/SCCM consensus conference proposed
broad defi nitions of sepsis and SIRS. Defi nitions of severe
sepsis, septic shock, hypotension, and MODS were also
offered. These broad defi nitions improved our ability to make
early detection of the disease possible, and allowed early ther-
apeutic intervention. In addition, the standardization of
research protocols improved the dissemination and applica-
tion of information derived from clinical studies. The pro-
posal was based on clinical and experimental results indicating
that a variety of conditions, both infectious and noninfectious
(i.e., burns, ischemia–reperfusion injury, multiple trauma,
pancreatitis), induce a similar host response. SIRS is consid-
ered to be present when patients have more than one of the
following clinical conditions: body temperature >38 °C or
<36 °C; heart rate > 90/min; respiratory rate >20/min or
PaCO 2 < 32 mmHg; leukocyte count >12,000/μl, <4,000/μl,
or >10 % immature (band) forms. Sepsis was defi ned as SIRS
in the presence of infection. However, in practice, the criteria
are very sensitive and nonspecifi c when they are used in the
diagnosis of burn-induced SIRS or sepsis. They even encom-
pass the vast majority of patients suffering extensive thermal
injury, which cannot refl ect the severity of the thermal injury
and weakens their value in clinical application.
Clinical results showed that patients were at of the SIRS
stage for 28 days in the fi rst month after suffering severe
burn injury; nearly one third of patients were diagnosed as
having sepsis, but most patients recovered without special
treatment. The Second Military Medical University of China
analyzed the contribution of the four factors (respiratory rate,
heart rate, temperature, and white cell counts) that were used
to diagnose SIRS to the development of organ dysfunction.
Multiple regression analysis was carried out between the
SIRS score and organ dysfunction score. Four factors made
different contributions to the occurrence of organ dysfunc-
tion, and they ranked in following order: respiratory rate,
heart rate, temperature, and WBC counts. The respiratory
rate is the most important factor in the occurrence of organ
dysfunction. According to these results, SIRS score system
was put forward as follows: body temperature >38 °C or
<36 °C, and/or leukocyte count >12,000/μl or <4,000/μl (1
point); heart rate >90/min (1 point), >120/min (2 points);
respiratory rate >20/min (1 point), 24/min (2 points), 28/min
(3 points). Patients with scores of ≤ 3 have mild SIRS;
patients with scores of ≥4 have severe SIRS [ 65 ].
In accordance with clinical practice, the First Affi liated
Hospital of the Chinese PLA General Hospital revised the
diagnostic criteria of sepsis proposed by the ACCP/SCCM
and put forward diagnostic criteria for burns sepsis [ 66 ]: sep-
sis is considered to be present when patients have a confi rmed
or suspected infection, and have two or more of the following
four clinical conditions plus any condition listed under the
fi fth clinical condition. SIRS is considered to be present when
patients have more than one of the following clinical fi ndings:
body temperature >39.0 °C or <35.5 °C, length of persistence
>3 days; heart rate >120/min; leukocyte count >12,000/μl,
or < 4,000/μl, and neutrophils percentage >0.80 or immature
granulocytes >10 %; respiratory rate >28/min; clinical symp-
toms and signs: mental depression, agitation, or delirious
speech; abdominal distension, diarrhea or alimentary tract
hemorrhage; tongue body purple, and dry.
In clinical practice, the revised diagnostic criteria for
SIRS and sepsis can refl ect the burn patients’ condition
exactly, and improve our ability to diagnose, monitor, and
treat burn-induced SIRS and sepsis.
14.4.2 Diagnostic Criteria of MODS
With large clinical trials and animal studies, the First Affi liated
Hospital of the Chinese PLA General Hospital proposed that the
complete diagnostic criteria of MODS should include the fol-
lowing three conditions [ 64 ]: presence of causative factors;
presence of SIRS; two or more organ systems involved. As there
is a lack of consensus on the diagnostic criteria of MODS in
China at present, morbidity and mortality of MODS vary widely
in different clinical studies. There is a tendency to stage diag-
nostic criteria and score illness severity. In this way, the dynamic
changes in organ functions can be refl ected, from normal func-
tion to dysfunction but compensation, then to decompensation.
Marshall’s multiple organ dysfunction score has been widely
used outside of China. Six organ systems were involved and
parameters refl ecting their functions were scaled from 0 to 4
points, with the maximum total score being 24 points. Normal
function scores 0 point, while organ failure scores 4 points. The
National Academic Conference on Critical Care Medicine of
China in 1995 passed the MODS staging diagnostic criteria and
illness severity score system (Table 14.1 ). Stage of organ dys-
function scores 1 point; early stage of organ failure scores 2
points; stage of organ failure scores 3 points [ 6 ]. As burns spe-
cialists participated in drawing up the diagnostic criteria, this
score system is also used to diagnose burns-induced MODS.
14.1 Predisposed Causes and Clinical Features of MODS

360
Table 14.1 Diagnostic staging criteria and illness severity score system for multiple organ dysfunction syndrome (MODS) in 1995
Organ systems
Clinical conditions
Score
Peripheral circulation
No hypovolemia; MAP ≈ 8.0 kPa; urinary output ≈ 40 ml/h; hypotension lasts more than 4 h
1
No hypovolemia; MAP: 6.7–8.0 kPa; urinary output: 20–40 ml/h; acra: cold or warm; no
consciousness disorders
2
No hypovolemia; MAP < 6.65 kPa; urinary output <20 ml/h; acra: cold or warm; confusion mostly
3
Cardiovascular
Tachycardia; body temperature increases 1 °C; heart rate increases 15–20 beats/min; normal
myocardial enzymes
1
Tachycardia; abnormal myocardial enzymes (CPK, AST, LDH)
2
Sinus tachycardia; ventricular fi brillation; II–III° AV conduction block; cardiac arrest
3
Respiratory
Respiratory rate: 20–25/min; PaO 2 : 8.0–9.3 kPa (inhaling air); PaO 2 /FiO 2 ≥ 39.9kPa; P(A-a)O 2
(FiO 2 1.0): 3.3–6.7 kPa; chest X-ray: normal. (Three of the fi ve clinical conditions)
1
Respiratory rate: >28/min; PaO 2 : 6.7–8.0 kPa (inhaling air); PaCO 2 < 4.7 kPa; PaO 2 /FiO 2 : 26.6–
39.9 kPa; P(A-a)O 2 (FiO 2 1.0): 13.3–26.6 kPa; chest X-ray: no consolidation of pulmonary alveoli
or consolidation ≤1/2 lung fi eld. (Three of the six clinical conditions)
2
Respiratory distress, respiratory rate: >28/min; PaO 2 ≤ 6.7 kPa (inhaling air); PaCO 2 > 6.0 kPa;
PaO 2 /FiO 2 ≤ 26.6 kPa; P(A-a)O 2 (FiO 2 1.0) > 26.6 kPa; chest X-ray: consolidation of pulmonary
alveoli ≥1/2 lung fi eld. (Three of the six clinical conditions)
3
Renal
No hypovolemia; urinary output ≈ 40 ml/h; urinary sodium, serum creatinine: normal
1
No hypovolemia; urinary output: 20–40 ml/h, urinary output may increase after using diuretics;
urinary sodium: 20–30 mmol/L; serum creatinine ≈ 176.8 μmol/L
2
No hypovolemia; anuria or oliguria (<20 ml/h lasting more than 6 h); urinary output does not
increase after using diuretics; urinary sodium >40 mmol/L; serum creatinine >176.8 μmol/L;
non-oliguria renal failure: urinary output > 600 ml/24 h, serum creatinine > 176.8 μmol/L, urine-
specifi c gravity ≤1.012
3
Hepatic
ALT >2-fold of normal value; serum bilirubin: 17.1–34.2 μmol/L (1.0–2.0 mg/dl)
1
ALT >2-fold of normal value; serum bilirubin >34.2 μmol/L (>2.0 mg/dl)
2
Hepatic encephalopathy
3
Gastrointestinal
Abdominal distention; diminished bowel sound
1
Severe abdominal distention; absent bowel sound
2
Paralytic ileus; hemorrhage of stress ulcer. (One of the two clinical conditions)
3
Coagulation
Blood platelet count < 100 × 10 9 /L; fi brinogen: normal; PT, TT: normal
1
Blood platelet count < 100 × 10 9 /L; fi brinogen: 2.0–4.0 g/L; PT, TT: about 3 s delayed than normal
value; euglobulin lysis test >2 h; no obvious generalized hemorrhage
2
Blood platelet count < 50 × 10 9 /L; fi brinogen <2.0 g/L; PT, TT: more than 3 s more delayed than
normal value; euglobulin lysis test <2 h; obvious generalized hemorrhage
3
Neurological a
Irritation or somnolence; eye opening response: opens to verbal command, speech, or shout; able
to talk; disoriented; obeys commands
1
Eye opening response: opens to pain; unable to talk, incoherent speech; withdraws from pain
2
Eye opening response: no response to speech; no response to painful stimulus
3
Metabolic
Blood glucose < 3.9 mmol/L or >5.6 mmol/L; serum sodium <135 mmol/L or >145 mmol/L;
pH < 7.35 or >7.45
1
Blood glucose < 3.5 mmol/L or >6.5 mmol/L; serum sodium <130 mmol/L or >150 mmol/L;
pH < 7.20 or >7.50
2
Blood glucose < 2.5 mmol/L or > 7.5 mmol/L; serum sodium < 125 mmol/L or > 155 mmol/L;
pH < 7.10 or >7.55
Each criterion should last for more than 12 h
3
MAP mean arterial pressure, CPK creatine phosphokinase, AST aspartate aminotransferase, LDH lactic dehydrogenase, AV atrioventricular, PaO 2 partial
pressure of oxygen, FiO 2 fracture of inspired oxygen, P(A-a)O 2 alveolar-arterial oxygen tension difference, PT prothrombin time, TT thrombin time
a Revised Glasgow Coma Scale
14.5
Preventative and Curative
Measures for MODS
In view of the predisposing complexity of the diversity and
pathogenesis of the cause of post-burn MODS, in recent
years, a number of units have explored the comprehensive
prevention and treatment measures, which have had good
effects. These can be summed up as follows.
14.5.1 Prevention and Treatment of
Shock Positively, Reducing
Early Organ Injury
The First Affi liated Hospital of the Chinese PLA General
Hospital proposed for the fi rst time the three goals of anti-
shock treatment, which were implemented in clinical prac-
tice, and obtained good therapeutic effects [ 68 ].
14 Postburn Multiple Organ Dysfunction

361
Goal 1 : The key to the prevention and treatment of shock
positively and reducing early organ injury is timely and
effective fl uid resuscitation. A number of resuscitation
formulas have been advocated, such as the Evans formula,
the Brooke formula, the Parkland formula, each having its
advantages and disadvantages. In China, the most popular
fl uid resuscitation formula is described as follows: in the
fi rst 24-h post-burn, the recommended crystalloid and
colloid volume is 1.5 ml/kg (%) total body surface area
(TBSA) and the recommended dextrose in water is
2,000 ml for adults; the ratio of crystalloid and colloid is
2:1. By cardiac catheter monitoring, we found that this
formula cannot meet the fl uid requirements, and by using
this formula, the hemodynamics of burned patients can-
not be maintained at normal levels. Thus, this formula
was modifi ed. The coeffi cient was increased from 1.5 to
1.8; the recommended dextrose level in water was
increased from 2,000 to 3,000 ml; the proportions of crys-
talloid and colloid are 1:1; 30 % of the amount adminis-
tered in the fi rst 3–4 h and 60–65 % of the amount
administered in the fi rst 8 h. By using this formula, the
urinary output reached 80–100 ml/h; hemodynamics such
as cardiac output, and the oxygen supply of tissue returned
to normal. Some people tried this in patients with delayed
resuscitation. Half of the total fi rst 24-h amount was
administered in the fi rst 2 h of resuscitation, and the total
fi rst 24-h amount increased by 30 %. Hypovolemic shock
could be corrected rapidly [ 67 – 69 ].
Goal 2 : to rapidly restore the blood supply to the gut. Gastro-
intestinal ischemia occurred early and recovered slowly
during the burn shock phase [ 70 ]. Even after full resusci-
tation was achieved and the shock symptoms were allevi-
ated, intramucosal pH (PHi) of burn shock patients was
still below 7.32, and would last for 2–3 days post-burn,
which means that the gastrointestinal tract was still in an
ischemic state [ 71 ]. Thus, anti-shock treatments must pay
attention to restoring blood supply to the gut. In major
burns patients, after proper fl uid resuscitation, anisoda-
mine 20 mg can be used, 3–4 times daily. The practice
proved that this medicine can dilate the contracted mesen-
tery blood vessel, increase the PHi value rapidly, alleviate
the mucous membrane damage, protect the intestine’s
mucous membrane barrier well, and prevent the endo-
toxin in the gut from entering the blood [ 72 , 73 ].
Goal 3 : prevention and treatment of oxygen free radical
damage. Fluid resuscitation enables tissue to restore the
blood supply; however, reperfusion can produce oxygen
free radicals and then lead to extensive oxidative injury.
Therefore, another goal of the anti-shock treatments is to
prevent oxygen free radical injury following reperfusion.
When fl uid resuscitation was carrying on, mannitol, vita-
min C and vitamin E combination therapy can be used
simultaneously to prevent oxygen free radical injury and
protect the function of the organs [ 74 – 76 ].
14.5.2 Early Excision and Closure
of the Burn Wound
The existence of a burn wound is the leading cause of all the
pathophysiological changes post-burn. Thus, erasing the
necrosis tissue as early as possible is an important measure
in reducing the absorption of toxins, preventing infection,
alleviating visceral dysfunction, and preventing MODS. In
the past, scholars in China usually considered that early exci-
sion should be carried out 4–7 days post-burn. In the First
Affi liated Hospital of the Chinese PLA General Hospital,
early excision has recently been carried out by 48-h post- burn,
which has a good effect on controlling infection, reducing
the level of endotoxin and cytokines, improving immune
function, reducing the metabolic rate, and protecting organ
functions [ 77 – 84 ]. If the patients’ condition permits, erasing
the burn wound as early as possible is the basic principle of
preventing MODS. Performing an operation while prevent-
ing shock is an important measure in successfully rescuing
deep burns patients admitted to hospital late, especially com-
bined with sepsis [ 83 , 85 ].
14.5.3 Rational Use of Antibiotics
As the sepsis induced by bacterial infection is the most com-
mon initiator of MODS, the application of antibiotics is essen-
tial. Antibiotics should be used routinely to prevent infection
during the shock phase and the perioperative period. Once
infection occurs, the appropriate choice of an antibiotic should
always be based on the results of bacterial cultures and the
drug sensitivity test. Medication time depends on the illness
severity. Antifungal agents should be used, if broad-spectrum
antibiotics have been used for more than 1 week [ 86 ].
14.5.4 Immunomodulation
The fi rst thing to do is to improve and restore the inhibited
immune system. As a traditional agent, which can improve
the nonspecifi c immune function of the body, immunoglobu-
lin is still in use now. α1 thymopeptide is considered to be an
ideal agent in the specifi c immune function, whose main pur-
pose is to promote the differentiation and maturation of lym-
phocytes and antigen presentation of mononuclear cells.
Yang et al. [ 87 ] found that α1 thymopeptide increased the
expression of HLA-DR in CD14 + monocytes and reduced
the apoptosis of the lymphocytes in peripheral blood. α1 thy-
mopeptide has been widely used in the treatment of severe
burns patients.
Second, the damage caused by the excessive infl ammatory
response must be controlled. Because the anti- infl ammatory
treatments, including specifi c antibodies and inhibitors to
pro-infl ammatory cytokines failed, medical workers turned to
14.1 Predisposed Causes and Clinical Features of MODS

362
other treatments. Studies have shown that ulinastatin can
antagonize the action of oxygen free radicals and various pro-
teases. In addition, as a serinase inhibitor, ulinastatin can also
inhibit blood coagulation system activation. Although the
ulinastatin has been on the domestic market for only a few
years, it has been accepted and widely used in the anti-infl am-
matory treatment of MODS (including burns sepsis) [ 88 – 90 ].
In recent years, hemofi ltration has been used in the treatment
of burns sepsis patients, and can effectively remove infl am-
matory mediators. Chai et al. found that the rational selection
of surgical timing and the application of hemofi ltration in
treating the major burns patients with sepsis signifi cantly
reduced the excessive infl ammatory response caused by
blood IL-1, IL-6, IL-8, and TNFα, stabilized hemodynamics,
increased arterial partial pressure of oxygen and oxygen satu-
ration, improved the symptoms caused by sepsis, and achieved
the valuable time for follow- up treatment [ 91 ].
14.5.5 Nutritional Support and Metabolic
Modulation
With regard to abnormal metabolism caused by a burn, we
proposed a number of strategies including emphasis on
intensive insulin therapy when using the growth hormone to
prevent and treat the hyperglycemia, promote protein synthe-
sis, and potassium supplying.
In large area deep burns, especially combined with sepsis,
the body is in stress, the blood glucose is elevated, all the
biological effects including the metabolism of fat, protein,
and sugar, the balance of water and electrolytes become
abnormal. This phenomenon is called insulin resistance and
causes serious metabolic disorder [ 92 ]. In the past, growth
hormone was used to promote protein synthesis, accelerate
wound healing, promote mucosal repair, which has benefi -
cial effects. However, the application of growth hormone can
also lead to a marked increase in the glycogen breakdown, an
increase in blood glucose via gluconeogenesis, and then,
cause hyperglycemia, which has adverse effects [ 93 , 94 ].
This modulates the metabolic disorder caused by severe
burn, takes full advantage of the benefi cial effects of growth
factor, and avoids the adverse effects. We proposed a new
strategy of intensive insulin therapy:
1. After suffi cient nutrition intake in severe burn or burn
sepsis, exogenous insulin should be used to meet the rela-
tive shortage of insulin in the body, which can reduce the
hypermetabolism of skeletal muscle protein by the mech-
anisms of ubiquitin–protein pathways, and promote pro-
tein synthesis, prevent the breakdown of fat, and reduce
the negative nitrogen balance.
2. Continuously pumping the insulin by using the insulin
pump and adjusting the dose by dynamic monitoring of
the blood sugar can effectively control the blood sugar
to the normal level, maintain the relative stability of sub-
stance metabolism and energy metabolism, and thus
correct the serious metabolic disorder caused by the
burn.
3. During the process of intensive insulin therapy promoting
protein and glycogen synthesis and inhibiting protein
hypermetabolism, large quantities of potassium in the
body are consumed causing low blood potassium.
4. Therefore, importance should be attached to the preven-
tion and treatment of hypokalemia and potassium should
be used to prevent the lethal complications of hypokale-
mia. After the application of the new strategy in severe
burns and burn sepsis, the negative nitrogen balance is
corrected, the blood sugar is brought under control, and
the
metabolic
disorder
is
effectively
corrected.
Simultaneously, hypokalemia and the harm caused by
hypokalemia are avoided.
14.5.6 Anticoagulation
After a severe burn, the system of coagulation is in a state of
hypercoagulability. Vascular endothelial cells are injured by
heat, infl ammatory mediators, and bacterial toxins, which
reduce the ability of anti-platelet adhesion of the surface of
the vascular endothelial cells; then, the dynamic equilibrium
among blood coagulation, anticoagulation, and fi brinolytic
systems is damaged and the coagulation system is activated,
leading
to
a
strong
tendency
toward
thrombosis.
Hypercoagulability and micro-thrombosis can cause sys-
temic and local wound injury. Systemic injury can cause
organ
microcirculatory
disturbances
that
lead
to
MODS. Thus, reducing blood coagulation abnormalities and
improving microcirculation are of great signifi cance.
However, in the past, little attention was paid to coagulation
abnormalities, especially in severe burns, combined burn–
blast injury, and sepsis. Once disseminated intravascular
coagulation (DIC) occurs, it is too late to use heparin and the
mortality rate is very high.
Through basic and clinical research, we proposed to
attach importance to early anticoagulant therapy after
burn injury and found that low molecular weight heparin
can be used to improve the hypercoagulable state. In clini-
cal practice, use indications for low molecular weight
heparin are: decreased platelet count (<100 × 10 9 /L) or
increased plasma d -dimer level. The prothrombin time
(PT) activated partial thromboplastin time (APTT) and
other indicators of abnormal coagulation are reference
indicators. Clinical application of low molecular weight
heparin corrected the hypercoagulability in severe burns
and burn sepsis, especially in combined burn–blast injury,
effectively avoiding the occurrence of DIC and the high
mortality [ 95 , 96 ].
14 Postburn Multiple Organ Dysfunction

363
14.5.7 Treatment of Sepsis Combined
with Hypernatremia
Burn sepsis is often accompanied by hypernatremia, which
does great harm to the body. High sodium concentration in
plasma causes continuing abnormality of plasma osmotic
pressure, which is closely related to central pontine myelin
damage. The changes in sodium ion concentration inside and
outside the cells induce aerobic glycolysis metabolic disor-
ders. The mechanism of hypernatremia is unclear, which
may be related to the abnormal distribution of sodium in the
body. Under such conditions, restricted sodium intake and
suffi cient water supply do not work. Mortality is higher than
80 %, especially when the sodium ion concentration
>160 mmol/L. Hypernatremia generally occurs suddenly
and progresses rapidly, and needs to be found and treated as
soon as possible. When shortening the period of the high-
sodium state of peripheral blood, attention should be paid to
avoiding dramatic changes in blood osmotic pressure, which
may result in tissue edema. Using anticoagulants in conven-
tional hemodialysis is fatally dangerous for patients with
severe burns, because:
1. Severe burns can cause destruction of blood cells, coagu-
lation abnormalities, etc.
2. Coagulation abnormalities can lead to surgical wound
bleeding, oozing, secondary infection of the wound, and
skin grafting failure.
3. Severely burned patients are prone to suffering from
stress ulcer, and coagulation abnormalities may cause
serious gastrointestinal bleeding.
By using heparin-free hemodialysis of hemophan adsorp-
tion to treat burn-sepsis patients with hypernatremia, we
found that its advantages include that:
1. It is convenient for fl uid replacement.
2. Internal environment and the balance of water and elec-
trolytes are controlled well.
3. It is useful in retaining hemodynamic stability.
4. It improves gas exchange.
Heparin-free hemodialysis of hemophan adsorption is
especially useful for critically ill patients who suffer from
hemodynamic instability, and need massive nutritional
support and fl uid replacement. Its relatively long treatment
time, by continuously detecting the sodium concentration
and changing the concentration of sodium ion replacement
fl uid, the concentration of sodium ions in the plasma is
gradually reduced until restored to physiological levels,
which can maintain a lower osmotic pressure difference
between blood and extracellular fl uid and between extra-
cellular fl uid and intracellular fl uid. This avoids the adverse
consequences caused by rapid changes of the osmotic
pressure of the blood and extracellular fl uid. In addition, as
hemophan with a positive ion can absorb the anticoagulant
heparin with a negative ion, the anticoagulant does not
enter the body, avoiding disturbance of the coagulation
system [ 97 ].
14.5.8 Protection and Support of
Organ Function
1. The protection and support of cardiac function
(a) While using cedilanid enhances myocardial contrac-
tility, fructose-1,6-diphosphate and Shenmai injec-
tion can be used to improve myocardial nutrition and
protect the heart function.
(b) Patients with delayed resuscitation need a large num-
ber of rapid infusions, which may cause increased
cardiac preload; if overloading occurs, furosemide
and mannitol should be used.
(c) If the cardiac afterload is overloaded, nitroglycerin
and sodium nitroprusside should be used to lower the
blood pressure.
For patients with sinus tachycardia, β-blockers
such as metoprolol or bisoprolol, with a longer
half- life, should be used to reduce cardiac work, rest-
ing energy expenditure, and skeletal muscle protein
catabolism.
2. Inhalation injury
We have raised the principle of hypoxia correction and
promotion of mucosal membrane repair. In clinical prac-
tice, the direction intervention is recommended:
(a) For patients suffering from inhalation injury and
severe head-and-neck burns, early tracheotomy is
used to ensure an unblocked airway. Once FiO 2 /
PaO 2 < 300, pure oxygen inhalation, epidermal growth
factor, and inhalation of Mucosolvan atomization,
vibrating expectoration drainage, airway lavage
drainage, and glucosteroid administration should be
given. If PaO 2 is lower than 70 mmHg, and fails to be
corrected by facial mask oxygen inhalation, respira-
tory support by the ventilator with positive end-
expiratory pressure (PEEP) should be given
immediately. Once the physiological indicators are
stable, weaning should be promptly attempted, in
order to avoid complications such as ventilator-
associated pneumonia (VAP).
(b) If protective ventilator strategy is raised, we should
pay more attention to satisfactory oxygen delivery
rather than simply high PaO 2 . The key points include
low tidal volume, low PEEP, low pressure control
ventilation, and permissive hypercapnia. We should
also weigh up both the synthetic effects of the
enhancement of PaO 2 by positive pressure ventilation
and the adverse effects from the potential reduction of
cardiac output. These strategies are applied in clinical
practice, hypoxemia has been corrected effectively
14.1 Predisposed Causes and Clinical Features of MODS

364
and mucosal membrane repair is promoted, with
avoidance of complications of ventilation, especially
in patients suffering from combined injury following
burn shock inhalation injury [ 12 , 85 , 95 ].
3. Protection of renal function
Effective circulatory volume should be resolved
early to reduce the duration of renal ischemia. Renal
failure can be prevented through urine alkalization and
diuresis, avoidance of renal toxicity agents, hemo-puri-
fi cation, and hemodialysis should be provided if neces-
sary, to maintain the homeostasis of the internal
environment.
4. Protection of liver function
In severe burns, hepatic impairment enjoys the feature
of early onset, long duration and slow recovery. In clinical
practice:
(a) Glutathione should be administered actively to avoid
injury caused by oxygen radicals.
(b) Branched-chain amino acid should be supplemented
to correct disturbance of the ratio of branched-chain
amino acid to aromatic amino acid.
(c) Hepatocyte growth factors should be applied to pro-
mote regeneration of hepatocytes, the production of
TNF mediated by endotoxin should be suppressed, to
protect the liver indirectly, and enhance the function
of the Kupffer cells.
(d) Administration of hepatoprotective agents, such as
glucurolactone, Essentiale N, etc.
5. Gastrointestinal protection and support
(a) Early enteral feeding. In addition to providing energy
for the body, early enteral feeding can also increase
gastrointestinal peristalsis, reduce intestinal perme-
ability, prevent the formation of dead space, then
prevent dysbacteriosis and bacteria endotoxin trans-
location. As long as there are no severe gastrointesti-
nal symptoms, early enteral feeding should be used.
If oral feeding is diffi cult, a duodenal feeding tube
should be used. For patients with extensive deep
burns, the First Affi liated Hospital of the Chinese
PLA General Hospital usually places an indwelling
duodenal feeding tube immediately when admitted,
which provides a good pathway for gastrointestinal
nutritional support. Nutritional support should be in
accordance with needs. This hospital produced its
own enteral nutritional emulsion called Fu Li Ru,
in which each 1,000 ml of the emulsion contains
500 kcal of thermal energy. One thousand to 3,000 ml
of emulsion can be used per day by oral administra-
tion or through a gastroduodenal tube.
(b) Prevention of stress ulcer. Prophylactic use of antacids
can increase the pH value of gastric acid, and reduce
the incidence of stress ulcer. Antacids include
H-histamine (N 2 ) receptor blocker (such as cimetidine
or ranitidine) and proton pump inhibitor (such as
omeprazole). The protective agents of gastric mucosa
can also be used. As a compound, sucralfate suspen-
sion has been widely used in clinical practice in recent
years, it cannot be absorbed by the gastrointestinal
tract, and it has less of an effect on gastric acid. Recent
studies indicated that an enteral or parenteral gluta-
mine supplement can relieve the gastrointestinal
mucosal injury, reduce hypermetabolism, and improve
immunity.
Conclusion
Overall, each unit has obtained varying degrees of treat-
ment effectiveness, after using the integrated control plan.
For example, the morbidity and mortality of MODS induced
by burns at the First Affi liated Hospital of the Chinese PLA
General Hospital were reduced from 17.3 to 6.9 % and from
87.5 to 40.0 % respectively [ 68 ]. However, it is worth point-
ing out that the pathogenesis of MODS is still not com-
pletely clear. At present, the method of preventing MODS
is mainly aimed at the inducement, not the process, of
infl ammatory reaction. Maybe this is the main reason why
the morbidity and mortality of MODS are so high. Thus,
there is still a massive amount of work for us to do.
References
1. Tilney HL, Bailey GL, Morgan AP. Sequential system failure after
rupture of abdominal aortic aneurysms unsolved problem in post-
operative care. Ann Surg. 1973;178(1):117–22.
2. Baue AE. Multiple, progressive, or sequential systems failure.
A syndrome of the 1970s. Arch Surg. 1975;110(7):779–81.
3. Eiseman B, Beart R, Norton L. Multiple organ failure. Surg Gynecol
Obstet. 1977;144(3):323–6.
4. Fry DE, et al. Multiple system organ failure. The role of uncon-
trolled infection. Arch Surg. 1980;115(2):136–40.
5. Sheng ZY, Hu S. Multiple organ dysfunction syndrome. Beijing:
Science Press; 1999. p. 1–5.
6. Wang JD, Wang BE. Multiple organ dysfunction syndrome
(MODS) score and the staging criteria. Chin Crit Care Med. 1995;
7(6):346–7.
7. Liu SC, Sheng ZY, Jia XM. Severe burn companied by MODS. Chin
Med J. 1983;63(8):518–20.
8. Sheng ZY, Hu S. Multiple organ dysfunction syndrome. Beijing:
Science Press; 1999. p. 6–9.
9. Zhang ML, Zhang PZ, Wang Y, et al. Invasive infection and multi-
ple organ dysfunction syndrome (MODS) in burns. Chin J Plast
Surg Burns. 1995;11:309–10.
10. Xie J, Xu SJ. The clinical analysis of severe burn injury compli-
cated with multiple organ dysfunction syndrome. J Hangzhou Med
College. 2001;22(5):260–2.
11. Tang P, Zhou ZY, Lou WZ, et al. Severe burn patients associated
with multiple organ failure. J Tianjin Med Univ. 1997;3(1):49–50.
12. Yang HM, Guo ZR, Sheng ZY, et al. Statistical analysis of the rela-
tions between the severe burn delayed resuscitation and the main
complications. Chin J Plast Surg Burns. 1994;10(2):164–5.
13. Hu S, Sheng ZY, Xue LB, et al. A clinically relevant model of mul-
tiple organ failure in the rabbits. Circ Shock. 1991;34(1):70A.
14. Hu S, Sheng ZY, Zhou BT, et al. A standardized and clinically
resemble model of multiple organ failure. Shock. 1995;3:S20.
14 Postburn Multiple Organ Dysfunction

365
15. Hu S, Sheng ZY, Zhou BT. A serialized study of animal models of
posttraumatic multiple organ dysfunction syndrome. Med J Chin
PLA. 1996;21(1):5–9.
16. Hu S, Sheng ZY, Zhou BT. A study of animal model of the delayed
two phase multiple organ dysfunction syndrome in goats. Chin J
Trauma. 1996;12(2):102–6.
17. Chen Y, Zhou M. Free radical medicine. Beijing: People’s military
medical press; 1989. p. 350–6.
18. Sheng ZY, Dong YL, Guo ZR, et al. Protective effects of antioxi-
dant drugs on liver and lung injury induced by intestinal ischemia.
Chin Med J. 1988;68(4):183.
19. Yang HM, Guo ZR, Sheng ZY, et al. Detection of oxygen free radi-
cals in visceral organs and scavenging effect of VitE and VitC in
seriously scalded rats with delayed fl uid resuscitation. Med J Chin
PLA. 1994;19(3):170–2.
20. Yang HM, Guo ZR, Zhu ZM, et al. Oxygen free radical injury after
delayed fl uid resuscitation in burn patients. Chin J Plast Surg Burns.
1993;9(5):359–62.
21. Wang GQ, Yu BJ, Liu ZG, et al. Apoptosis of liver cells from
burned rats with delayed fl uid resuscitation. Chin Crit Care Med.
1999;11(10):581–3.
22. Wang GQ, Yu BJ, Xia ZF, et al. Myocardial apoptosis induced by
delayed fl uid resuscitation in a burned rat model. Chin J Burns.
2000;16(1):40–2.
23. Zhang C, Sheng ZY, Hu S, et al. Translocation of intestinal endotoxin
and bacteria induced by the apoptosis of enterocytes in scald rats after
delayed resuscitation. Chin Crit Care Med. 1999;11(10):581–3.
24. Yang HM, Guo ZR, Sheng ZY, et al. Delayed fl uid resuscitation
induced bacterial translocation after lethal thermal injury: role of
oxygen free radical injury of intestinal mucosa. Chin Med
J. 1994;74(9):552–5.
25. Yang HM, Guo ZR, Sheng ZY, et al. Oxygen free radical injury and
its relation to endotoxin translocation after delayed fl uid resuscita-
tion in burn patients: a prospective study. Chin J Trauma. 1995;
11(3):158–60.
26. Yang HM, Sheng ZY, Guo ZR, et al. Oxygen free radical injury and
its relation to bacterial and endotoxin translocation after delayed
fl uid resuscitation: clinical and experimental study. Chin Med
J. 1997;110(2):118–24.
27. Yang HM, Shi ZG, Chang D. The mechanism of delayed resuscita-
tion on intestinal bacteria endotoxin translocation. Chin J hospital
infection. 1994;4(4):201–5.
28. Yao YM, Sheng ZY. The modern understanding of sepsis related
signal pathway. Chin Crit Care Med. 2003;15(1):3–6.
29. Li HY, Yao YM, Yao S, et al. Potential role of JAK/STAT in regulat-
ing toll-like receptor 2 gene express ion in rats with postburn staph-
ylococcus aureus sepsis. Chin Crit Care Med. 2003;15(3):139–42.
30. Li HY, Yao YM, Shi ZG, et al. The potential role of staphylococcal
enterotoxin B in rats with postburn Staphylococcus aureus sepsis.
Shock. 2003;20(3):257–63.
31. Yao YM, Sheng ZY. Relationship of staphylococcus aureus exo-
toxin with sepsis and multiple organ injury. Chin J Trauma.
2004;20(12):711–4.
32. Yao YM, Xu S, Sheng ZY. Advances in high mobility group box-1
protein mediated multiple organ dysfunction and its potential inter-
ventional strategies. Acta Acad Med Sin. 2007;29(4):459–65.
33. Fang WH, Yao YM, Shi ZG, et al. The signifi cance of changes in
high mobility group-1 protein mRNA expression in rats after ther-
mal injury. Shock. 2002;17(3):329–33.
34. Li HY, Yao YM, Shi ZG, et al. Signifi cance of changes in high
mobility group-1 protein in rats with postburn Staphylococcus
aureus sepsis. Chin J Exp Surg. 2001;18(4):336–7.
35. Dong N, Yao YM, Yu Y, et al. Changes in plasma high mobility
group box-1 protein levels and its relationship with sepsis in
severely burned patients. Acta Acad Med Sin. 2007;29(4):466–70.
36. Zhang LT, Yao YM, Lu JQ, et al. Sodium butyrate prevents lethality
of severe sepsis in rats. Shock. 2007;27(6):672–7.
37. Hu S, Sheng ZY, Zhou BT, et al. The “diphasic preexcitation”
theory of Post-traumatic multiple organ failure. Med J Chin PLA.
1995;20:361.
38. Bone RC, Newton SI. Sepsis, SIRS, and CARS. Crit Care Med.
1996;24:1125.
39. Yang HM, Yu Y, Chai JK. Study on the relationship between the
human leucocyte antigen-DR expression on CD14 + monocytes and
sepsis. Chin J Burns. 2007;24(4):272–5.
40. Dong N, Yao YM, Jin BQ, et al. CD14The correlation between
CD14 gene polymorphism and prognosis and human leukocyte
antigen DR expression in patients with major burns. Chin J Trauma.
2006;22(8):565–9.
41. Hu S, Sheng ZY, Liang YJ, et al. Feeding E. coli plus severe
hypovolemic shock induces gut origin sepsis and multiple organ
dysfunction syndrome in rabbits. Chin Crit Care Med. 1998;10(10):
587–91.
42. Lv Y. Expression of infl ammatory mediators and ICAM-1 in lung
tissue after gut ischemia reperfusion in rats. Chin J Emerg Med.
2003;10(10):670–2.
43. Cao WH, Hu S, Sun D, et al. Replication of an animal model of
partial ischemia and reperfusion injury of intestine. J Traumatic
Surg. 2005;7(1):46–9.
44. Hu S, Jin H, Lv Y, et al. Changes in gastrointestinal intra-mucosa
pH of goat following hypovolemic shock and resuscitation. Chin
Crit Care Med. 1997;9:708–10.
45. Cao WH, Hu S, Bai YM, et al. The mechanism of apoptosis of
peripheral blood PMN induced by partial ischemia and reperfusion
of intestine. Infect Infl amm Repair. 2004;5(3):103–6.
46. Lv Y. Analysis of the poly-genes expression changes in liver by
gene expression profi le chip in gut ischemia-reperfusion rats. Chin
Crit Care Med. 2003;15(2):84–7.
47. Hu S. Review and prospect of multiple organ dysfunction syndrome
research. Chin J Burns. 2001;17(2):136–8.
48. Xia B, Jin FS, Hu S, et al. Effects of intestine ischemia-reperfusion
on the tolerance of gut following early enteral nutrition. Acta Acad
Med Militaris Tertiae. 2005;27(10):1016–9.
49. Yao YM, Chai JK, Lin HY. Theory and practice of modern sepsis.
Beijing: Science Press; 2005. p. 362–83.
50. Shi FS, Luo XD, Yang ZC. Cell apoptosis after burn injury and
multiple organ dysfunction syndrome (MODS). Foreign Medicine
Health. 2000;21(5):262–7.
51. Yao YM, Chai JK, Lin HY. Theory and practice of sepsis. Beijing:
Science Press; 2005. p. 402–681.
52. Chai JK, Gao JC, Guo ZR, et al. Sequential changes in energy
expenditure in severely burned patients with sepsis. Med J Chin
PLA. 1999;24(2):88–90.
53. Li ZL. Modern critical care medicine. Hefei: Anhui Science and
Technology Press; 1998. p. 209–22.
54. Chai JK, Diao L, Sheng ZY, et al. Experimental study on the
mechanisms of enhancement of aerobic glycolysis of muscles in
burns and sepsis the verifi cation of the existence and the
enhancement of the aerobic glycolysis of muscles in early
postburn period and sepsis. Chin J Plast Surg Burns. 1999;15:
49–52.
55. Chai JK, Diao L, Sheng ZY, et al. Impact of intracellular Na +
concentration alteration on intracellular aerobic glycolysis in
skeletal muscles in sepsis. Natl Med J China. 1999;79:546–8.
56. Chai JK, Diao L, Sheng ZY, et al. Experimental study on the
enhancement of aerobic glycolysis of muscles in sepsis and its
relationship with the activity of the intracellular Na + , K + , ATPase.
Acad J PLA Postgrad Med Sch. 1999;20(2):89–91.
57. Chai JK, Wu YQ, Sheng ZY. Role of ubiquitin proteasome pathway
in skeletal muscle wasting in rats with endotoxemia. Crit Care Med.
2003;31(6):1802–7.
58. Chai JK, Wu YQ, Sheng ZY. The relationship between skeletal
muscle proteolysis and ubiquitin proteasome proteolytic pathway
in burned rats. Burns. 2002;28(6):527–33.
References

366
59. Chai JK, Wu YQ, Sheng ZY. Transcriptional expression of ubiqui-
tin activating enzyme in skeletal muscle of burn rats. Chin J Surg.
2002;40(1):72.
60. Chai JK, Wu YQ, Sheng ZY. Study on the changes in ubiquitin and
ubiquitinated protein in rat skeletal muscle during postburn period.
Med J Chin PLA. 2002;27(7):608–9.
61. Chai JK, Wu YQ, Sheng ZY. Effect of sepsis on proteolytic rate of
different kinds of skeletal muscle in rats and investigation of its
possible mechanism. Chin Crit Care Med. 2001;13(5):272–4.
62. Chai JK, Shen CA, Yao YM. The change of skeletal muscle prote-
olysis in severely burned patients with sepsis and study on its mech-
anism. Med J Chin PLA. 2002;27(9):774–6.
63. Chai JK, Shen CA, Sheng ZY. Changes in skeletal muscle protein
metabolism in burned rats with sepsis and the role of glucocorticoid
in skeletal muscle proteolysis. Chin J Surg. 2002;40(9):705–8.
64. Hu S, Sheng ZY, Lin HY. Investigation of the early diagnosis and
early warning indicators of multiple organ dysfunction syndrome.
Med J Chin PLA. 1996;21(1):13–160.
65. Wang GQ, Xia ZF, Chen YL, et al. The relationship between sys-
temic infl ammatory response syndrome and organ dysfunction in
severely burned patients: clinical signifi cance of systemic infl am-
matory response syndrome score. Chin Crit Care Med. 1999;
11(12):725–7.
66. Chai JK, Sheng ZY, Gao JC, et al. The characteristics and prognosis
is of 111 burn patients with sepsis. Chin Crit care med. 1999;11(12):
721–4.
67. Sheng ZY. Prevention and treatment of severe burn induced multi-
ple organ dysfunction syndrome. J Traumatic Surg. 2001;3(1):1–3.
68. Sheng ZY, Yang HM, Chai JK, et al. Prevention and treatment of
MODS in severely burned patients: an institute based retrospective
study. Chin J surg. 2000;38(6):435–8.
69. Yang HM, Chai JK, Sheng ZY, et al. Effect of improved resuscita-
tion regime on the outcome of severely burned patients with delayed
fl uid resuscitation. Chin Crit Care Med. 2000;12(10):610–2.
70. Cui XL, Sheng ZY, Guo ZR, et al. Study of gastrointestinal mucosa
ischemia in severe burn shock. Chin J Plastic Surg Burns.
1998;14:262–5.
71. He LX, Guo ZR, Gao WY, et al. Signifi cance of the application of
anisodamine in shock period in severe burn patients. Med J Chin
PLA. 1997;22(1):43–5.
72. Sheng CY, Gao WY, Gou ZR, et al. Anisodamine restores bowel
circulation in burn shock. Burns. 1997;23:142–6.
73. Chai JK, Sheng ZY, Zhu ZM. The effect of antioxidants on neutro-
phil function after burns. In: Sheng ZY, Zhu ZM, editors. Advances
in burns. 1st ed. Beijing: International Academic Publishers; 1992.
p. 93–102.
74. Yang HM, Sheng ZY, Guo ZR, et al. Effect of delayed resuscitation
on oxygen free radical in burn rat liver and kidney and vitamin E
and vitamin C treatment effects. Med J Chin PLA. 1994;9:170–3.
75. Chai JK, Yang HM, Sheng ZY, et al. Anisodamine in prevention
and treatment of sepsis of severely burned patients. Chin J Surg.
2000;38(9):686–9.
76. Chai JK, Guo ZR, Sheng ZY, et al. Protective effects of vitamin E
on impaired neutrophil phagocytic function in patients with severe
burn. Chin J Plast Surg Burns. 1995;11(1):32–5.
77. Guo ZR, Sheng ZY, Diao L, et al. Large area burn escharectomy
during shock stage. Chin J Plast Surg Burns. 1993;9:5–8.
78. Guo ZR, Sheng ZY, Gao WY, et al. Escharectomy during burn
shock stage contributed to controlling or alleviating infectious
complication. Chin J Surg. 1995;33:406–8.
79. Guo ZR, Sheng ZY, Diao L, et al. Extensive wound excision in the
acute shock stage in patients with major burns. Burns. 1995;
21:139–42.
80. Chai JK, Guo ZR, Sheng ZY, et al. Performing escharectomy
following “clinical guidelines” in extensively burned patients
during burn shock stage. Chin J Plast Surg Burns. 1999;15(4):
289–91.
81. Wang ZT, Yao YM, Sheng ZY. Effect of escharectomy during
shock stage on plasma high mobility group box protein 1 levels
and multiple organ dysfunction in burned rats. Med J Chin PLA.
2005;30(10):864–6.
82. Chai JK, Sheng ZY, Yang HM, et al. Successful treatment of inva-
sive burn wound infection with sepsis in patients with major
burns. Chin Med J. 2000;113(12):1142–6.
83. Chai JK, Sheng ZY, Guo ZR, et al. The experience of the manage-
ment of burn sepsis with different strategies in our department
during the past 29 years. Chin J Burns. 2000;16(2):78–81.
84. Chai JK, Guo ZR, Zhu ZM, et al. Clinical and experimental study
on quantifi cation of subeschar bacteria. Chin J Plast Surg Burns.
1992;8(2):97–9.
85. Chai JK, Sheng ZY, Yang HM, et al. Treatment strategies for mass
burn casualties transferred from a distance-clinical experience.
Wehrmedizin Und Wehrpharmazie. 2005;2:58–60.
86. Chai JK. The importance of rational antibiotic use for severe burn
patients. Chin J Burns. 2003;19(Suppl):61–2.
87. Yang GX, Yang HM, Hu S. Infl uence of thymosin α1 on expres-
sion of monocyte in scald rats with delayed fl uid resuscitation.
Infect Infl amm Repair. 2007;8(2):92–4.
88. Hu XH, Zhang HY, Ge YL, et al. Protective effects of ulinastatin
against multiple organic damage after severe burn injury:
experimental and clinic studies. Chin Med J. 2005;85(41):
2889–94.
89. Xu YB, Qi SH, Xie JL, et al. Protective effects of ulinastatin on
organ function in patients with severe burn. Chin Crit Care Med.
2006;18(1):39–41.
90. Cao WH, Chai JK, Yang HM, et al. The infl uence of high dose
ulinastatin on blood coagulation function in severely burned
patients and its signifi cance. Infect Infl amm Repair. 2005;6(3):
162–4.
91. Chai JK, Shen CA, Li JJ, et al. Effects of hemofi ltration on infl am-
matory mediators in peripheral blood of patients with burn sepsis.
Chin Med J. 2001;81(15):943–4.
92. Chai JK, Diao L, Hao DF, et al. Dynamic changes in metabolism
in sheep after thermal injury and in sepsis. Chin J Surg. 2001;
39(7):548–52.
93. Chai JK, Hao DF, Guo ZR, et al. Effect of recombinant human
growth hormone therapy on hypermetabolism postburn. Med
J Chin PLA. 1999;24(6):417–9.
94. Chai JK, Hao DF, Wu YQ, et al. Severe burned patients after sur-
gery: recombinant human growth hormone therapy its metabolic
effects. Chin J Surg. 2002;40(2):107–11.
95. Chai JK, Sheng ZY, Lu JY, et al. Characteristics of and strategies
for patients with severe burn-blast combined injury. Chin Med
J. 2007;120(20):1783–7.
96. Li F, Chai JK, Yang HM, et al. Effect of low molecular weight
heparin on hypercoagulability in extensive severe burn casualties.
Med J Chin PLA. 2007;32(12):1218–9.
97. Chai JK, Diao L, Sheng ZY, et al. Heparin-free hemodialysis in
the treatment of hypernatremia in severely burned patients. Burns.
2000;26:634–7.
14 Postburn Multiple Organ Dysfunction

367
Z. Yang, Chinese Burn Surgery, DOI 10.1007/978-94-017-8575-4_15,
© Springer Science+Business Media Dordrecht and People’s Medical Publishing House 2015
15.1
Hypermetabolism in Burns
Shiliang Wang
Burn hypermetabolism is characterized by an elevated meta-
bolic rate, increased protein catabolism, and energy con-
sumption. Hypermetabolism in severe burn patient could last
several weeks or longer; it is one of the most significant reac-
tions of homeostasis. In view of this, since the 1980s, the
Burns Institute of the Southwest Hospital (BISH) at the
Third Military Medical University (TMMU) has investigated
the general trends and rules of energy expenditure, devel-
oped a formula to calculate calorie needs in Chinese adult
burn victims and the relationships between energy expense
and burn area, depth, phase, prognosis, putting forward a
proposal that is different from the conventional ebb and flow
phase, studied the proportion of energy expense among glu-
cose, fat, and protein, and advanced a new theory, “enterog-
enous hypermetabolism” and its modulation [1–3].
15.1.1
Study of Energy Expenditure
Regularities in Chinese Adult Burn
Victims
15.1.1.1 Energy Needs in Adult Burn Victims,
the Relationship Among Resting
Energy Expenditure and Burn Area,
Depth, Phase, Operation,
and Prognosis [4–6]
In BISH at TMMU, oxygen consumption, carbon dioxide
production, and urinary nitrogen were measured in 75 burn
adults on post-burn day (PBD) 1, 2, 3, 7, 14, 21, 28, and in
13 normal adults as controls. Burns covered 5–98  %
(44 ± 27.2 %) of the total body surface area (TBSA), and the
victims were aged 16–51 years (31.2 ± 9.9 years), 53 were
male and 22 were female out of 75 cases. For burn areas less
than 60  %, resting energy expenditure (REE) clearly
increased, as burn area increased with an almost linear
­relationship between burn area and REE. When the extent of
the burn area was greater than 60 %, REE did not increase or
decrease as the burn area increased (Fig. 15.1). As listed in
Table 15.1, if the total area of burn was similar, and the third-­
degree burn was larger, the metabolic rate was markedly
increased. The metabolic rate was quite different during
varying time phases post-burn, its general trend was to
increase gradually throughout the course of the burns, the
peak value of REE was during PBD 7–21, and was progres-
sively reduced, keeping pace with the closure of the burn
wound. The dynamic curve of REE variation in the burn area
of 5–98 % along with time phase was an arched curve, the
back of the arch went upward (Fig. 15.2). The differences in
the peak phase of the metabolic rate were accompanied by
the variation in the burn area. In patients with a small burn
area, the phase peak came earlier and was shorter, while the
peak came later and was sustained for longer in large burn
areas. In Fig. 15.3 and Table 15.2, on PBD 1 the REE in the
>71 % burn group was lower than in the other three <70 %
Metabolism in Burns
Shiliang Wang and Shilin Deng
15
80
(334.7)
(10)
(10)
(7)
(6)
REE [Kcal (kJ) / (m2 • h)]
(9)
Burn area (% total body surface)
Tendency line
Measured line
(7)
10
20
30
40
50
60
70
80
90
100
0
(6)
(4)
(6)
(4)
75
(313.8)
70
(292.9)
65
(272.0)
60
(251.0)
55
(230.1)
50
(209.2)
45
(188.3)
Fig. 15.1  The curved linear relationship between resting energy
expenditure (REE) and extent of burn during post-burn day (PBD 1–28)

368
burn groups, and increased faster than other groups after the
early phase. The peak of this group at PBD 21 (326.2 ± 27.6)
kJ/(m2·h) was twice the normal value, and still retained
318.8 ± 26.8 kJ/(m2·h) on PBD 28; on PBD 1 the REE in the
<30 % burn group increased to (215.1 ± 25.9) kJ/(m2·h), the
peak (233.5 ± 29.0) kJ/(m2·h) during PBD 7–14 was 1.4
times the normal value, and decreased to (201.7 ± 21.8) kJ/
(m2·h) on PBD 21; the REE peak value of the 31–50 % burn
group was (277.8 ± 28.0) kJ/(m2·h) on PBD 14, and 1.7 times
the normal value; the REE peak value of the 51–70 % burn
group on PBD 14–21 was (299.6 ± 9.9) kJ/(m2·h), 1.8 times
the normal value. It always indicates an unfavorable progno-
sis if the value of REE is lower throughout the whole burn
course or suddenly decreases after increasing in severe burns
(Table 15.2).
In addition, the comparison of REE variation between the
survival group and the death group was studied in the BISH
at TMMU (Table 15.3).
The Institute for Burns Research of the 4th Hospital in
Tianjin performed a study of 45 adult burns victims involv-
ing 20–93 % (46.4 ± 9.1) of the TBSA to monitor and ana-
lyze dynamically the variation in the REE using a metabolism
cart (MedGraphic, St Paul, MN, USA) in 1995–1997. Results
showed that the energy expenditure (EE) of the burn shock
stage was obviously higher than the value predicted by
Harris-Benedict (HB formula, but did not reach a peak,
which is usually on PBD 5–9 with the mean of PBD 6.7. EE
of the <30 % TBSA group decreased rapidly to a low level
after reaching a peak, while the >70 % TBSA group main-
tained a high level after reaching the peak. However, none of
the groups were able to recover to the pre-burn EE level
when the wound was closed. In addition, the value of REE
was related to the factors of the burn area, e.g., depth, inhala-
tion injury, operation. Meanwhile, the energy supplementa-
tion of 45 burns cases was divided into three groups, i.e.
1.0 × REE, 1.2 × REE, and 1.5 × REE. The result showed that
the variation in the metabolic index, hormone level, and
serum aminogram of the 1.2 × REE group was the best among
the three groups, considering that the energy supplementa-
tion of 1.2 × REE in burn adults was more rational [7, 8].
The Institute for Burn Research of the 304 Hospital of the
PLA studied the effect of deep wound excision and skin
grafting within 48 h post-burn (shock stage) on REE changes.
Results showed that the increasing scope of REE in the deep
burn excision and skin grafting within the shock stage (SS)
group was obviously lower than in the burn excision and
grafting after the shock stage (ASS) group (Table 15.4) [9].
Table 15.1  The relationship between resting energy expenditure (REE) and third degree burns x
s
±
(
)
Group (n)
1(7)
2(6)
3(6)
4(4)
Burn area (%)
66.0 ± 18.5
59.0 ± 18.2
62.0 ± 6.0
65.0 ± 16.0
Third-degree burn area (%)
12.7 ± 9.5
20.3 ± 5.6
39.6 ± 5.2
54.5 ± 4.6
REE (kcal/m2 · h)
62.9 ± 6.5
66.5 ± 4.9
69.9 ± 4.6
71.1 ± 5.5
REE (kJ/m2 · h)
263.2 ± 27.2
278.2 ± 20.5
292.5 ± 19.2#
310.1 ± 23.1#,&
*No significant differences in the burn area, but significant differences in REE between groups 1 and 3, groups 1 and 4, and groups 2 and 4 (all
p < 0.05); # vs group 1 p < 0.05; & vs group 2 p < 0.05
75
(313.8)
(64)
(59)
(59)
0
1
2
7
3
PBD
Tendency line
Measured line
14
21
28
(60)
(62)
(58)
(54)
70
(292.9)
65
(272.0)
60
(251.0)
55
(230.1)
50
(209.2)
45
(188.3)
40
(167.4)
REE [Kcal (kJ) / (m2 • h)]
Fig. 15.2  The dynamic phase curve of REE in adults with burns
involving 5–98 % of the total body surface
80
(334.7)
75
(313.8)
70
(292.9)
65
(272.0)
60
(251.0)
55
(230.1)
50
(209.2)
15
(188.3)
>71 %
51–70 %
31–50 %
<30 %
0
1
2
3
7
14
PBD
21
28
REE [Kcal (kJ) / (m2 • h)]
Fig. 15.3  The dynamic phase curve of REE in each extent of burn
group
15  Metabolism in Burns

369
The Burn Institute of the 304 Hospital considered the
energy supplementation in adult burn victims to be
REE × (1.1–1.3).
15.1.1.2 Phase of Burn Metabolism [5, 6, 10]
Cuthbertson began his pioneering work characterizing the
ebb and flow phases of the metabolic response to injury.
During the early phase (ebb phase) of the injury, there is a
decrease in REE.  The question of how to understand the
“ebb phase” still remains, especially in China. Seventy-five
burn adults were divided into different burn area groups in
the BISH at the TMMU. They found none of the group’s
REE to be lower than normal; the lowest REE was found in
the group with a burn area that covers 90–100  % of the
TBSA on PBD 1. The REE (173.6 ± 10.1 kJ, 41.5 ± 2.4 kcal/
m2·h) is not lower than the normal value (162.8 ± 9.2 kJ,
38.9 ± 2.2 kcal/m2·h). Therefore, in light of energy metabo-
lism “ebb phase,” whether the “ebb” of the ebb phase was
considered to be a “decrease,” “depression,” or “ebb tide,”
these words are all not in keeping with the metabolic energy
changes during the early stage after burns. The metabolic
rate was not decreased and only increased a little in the early
Table 15.2  Various phasic REE [kJ (kcal)/(m2 · h), ± s] in different burn area groups
Burn area (%)
Post-burn day
1
2
3
7
14
21
28
30 %
215.1 ± 25.9
219.1 ± 24.3
226.8 ± 30.5
231.4 ± 23.8
233.5 ± 28.9
213.0 ± 22.2
201.7 ± 21.8
(51.4 ± 6.2)
(51.9 ± 5.8)
(54.2 ± 7.3)
(55.3 ± 5.7)
(55.8 ± 6.9)
(50.9 ± 5.3)
(48.2 ± 5.2)
(n = 23)
(n = 23)
(n = 21)
(n = 24)
(n = 21)
(n = 18)
(n = 15)
50 %
228.5 ± 24.3
238.1 ± 20.9
256.9 ± 29.6
266.1 ± 29.7
277.8 ± 28
264.8 ± 25.1
230.5 ± 40.6
(54.6 ± 5.8)
(56.9 ± 5.0)
(61.4 ± 6.6)
(63.6 ± 7.1)
(66.4 ± 6.7)
(63.3 ± 6.0)
(55.1 ± 9.7)
(n = 9)
(n = 10)
(n = 13)
(n = 14)
(n = 13)
(n = 13)
(n = 12)
70 %
220.5 ± 24.3
236.8 ± 20.1
264.4 ± 29.7
283.3 ± 25.9
298.3 ± 28
299.6 ± 28
299.1 ± 28.5
(52.7 ± 5.8)
(56.6 ± 4.8)
(63.2 ± 7.1)
(67.7 ± 6.2)
(71.3 ± 6.7)
(71.6 ± 6.7)
(66.7 ± 6.8)
(n = 10)
(n = 12)
(n = 13)
(n = 14)
(n = 16)
(n = 15)
(n = 15)
100 %
179.5 ± 25.9
211.7 ± 22.6
235.6 ± 17.6
282.4 ± 17.2
301.7 ± 23
326.2 ± 27.6
318.8 ± 26.8
(42.9 ± 6.2)
(50.6 ± 5.4)
(56.3 ± 4.2)
(67.5 ± 4.1)
(72.1 ± 5.5)
(77.97 ± 6.6)
(76.2 ± 6.4)
(n = 17)
(n = 14)
(n = 13)
(n = 12)
(n = 12)
(n = 12)
(n = 12)
c,e,f
a,b,e,f
a,b,e,f
a,b,c
a,b,c,e
a,b,c,d,e,f
a,b,c,d,e,f
a~30 % vs ~50 % p < 0.05
b~30 % vs ~70 % p < 0.05
c~30 % vs ~100 % p < 0.05
d~50 % vs ~70 % p < 0.05
e~50 % vs ~100 % p < 0.05
f~70 % vs ~100 % p < 0.05
Table 15.3  The comparison of REE in the survival and death groups x
s
±
(
)
Group
Burn area %
Third-degree area %
REE [kJ(kcal)/(m2·h)]
Compared with normal value
Comparison between two groups
Survival (n = 8)
88 ± 4.5
36 ± 27.8
242.3 ± 12.1
p < 0.001##
p < 0.001&
(82–93)
(10–75)
(57.9 ± 2.9)
Death (n = 7)
90 ± 5.0
58 ± 21.0
170.7 ± 18.8
p > 0.05#
(85–98)
(18–80)
(40.8 ± 4.5)
*Normal value of REE is 162.8 ± 9.2 kJ (38.98 ± 2.22 kcal/m2·h) (n = 13); # vs normal value p < 0.05; ## vs normal value p < 0.001; & vs death group
p < 0.001
Table 15.4  Changes in REE [kcal/(m2 · h)] in the shock stage (SS) and the after the shock stage (ASS) group
Group
PBD
0
1
2
3
5
7
14
21
28
Excision and
grafting in SS
(n = 15)
39.2 ± 1.8
(n = 8)
45.7 ± 2.3
(n = 11)
43.3 ± 2.0
48.5 ± 3.1*
56.8 ± 3.3*
65.6 ± 4.1*
74.2 ± 3.6*
75.3 ± 4.2
59.8 ± 3.6
Excision and
grafting in ASS
(n = 6)
_
46.1 ± 1.9
(n = 4)
48.9 ± 2.4
(n = 5)
57.6 ± 2.7
(n = 5)
64.5 ± 2.9
73.8 ± 3.0
82.4 ± 3.9
77.1 ± 4.6
61.2 ± 4.1
*vs REE of wound excision in the ASS group, p < 0.05; normal value of REE in adults 38.5 ± 2.1 kcal/m2·h
PBD post-burn day
15.1  Hypermetabolism in Burns

370
phase post-­burn. Second, on PBD 1, 2, and 3, it was in direct
proportion to the REE <60 % of the TBSA to burn area.
While the burn area was more than 60 % of the TBSA, the
larger the burn area, the less the scope of the REE increased.
That is to say, in the more than 60 % of the TBSA group, the
REE is increased along with burn area during PBD 7–28,
and on PBD1, 2, and 3 the larger burn area, had the lower
REE value (Fig.  15.4). This was because of the REE of
moderate and minor burns being clearly increased in the
early phase post-­burn, while the REE of the large area burns
increased slowly during the early stage after the burn.
Moreover, according to ours and other data (e.g., Chinese
Journal of Plastic and Burn Surgery, 1985,1(2):6–9), no
matter whether burns patients or animals, the plasma corti-
sol, glucagon, and urinary catecholamine were all higher
than normal, although it was not clearly higher and usually
not lower than normal. Therefore, we divided the burn meta-
bolic phase into the “slow rising phase” and the “fast rising
and hyper- phase.” The “slow rising phase” means a short
duration of slowly increasing REE during the shock or post-
burn short stage after burn injury. This phase is obscure in
minor burns, and about 3 days long in large area burns. It is
distinct from the usual “ebb phase.” Certainly, it should be
tested and verified by more data if this dividing phase is
reasonable.
15.1.1.3 Formula for Estimating REE in Chinese
Adult Burn Victims [5, 6, 10]
Since the 1970s the most popular formulas for the estimating
EE of adult burn victims in China were the Curreri formula
and the HB equation. Because no burn factor was included in
the HB equation, in addition to several burn centers using the
metabolic cart, most of the burns units in China usually used
the Curreri formula to estimate energy supplementation.
At the end of the 1980s, by measuring the REE of 105 burn
patients and normal adults, the BISH at the TMMU worked out
the first formula for estimating REE in Chinese adult burn vic-
tims (TMMU formula), i.e., the energy supplementation of an
adult burn victim is: kcal(kJ)/day = 1, 000  (4, 184) × m2(body sur-
face  area)  +  25  (104.6)  ×  % (body  surface  area  burned).
Compared with the conventional Curreri formula, etc., calculat-
ing the basic energy requirement of the TMMU formula is more
reasonable because the variation of metabolic rate is in propor-
tion to the body surface area, and out of proportion to the body
weight. In a study of animals with different body surface areas, it
was proved that in a comparison of the metabolic rate among the
different burn areas, regardless of the total area of the body sur-
face of large or small animals, the energy expenditure per square
meter of the body surface area over 24  h is almost around
1,000 kcal (4,184 kJ), and the metabolic rate per kilogram of
body weight in small animals is much higher than in the large
animals.
Certainly, the energy expenditure of the body surface area
per square meter is also affected by age, sex, sleep, feeding,
and mental state, etc. Usually, we use the following equation
to calculate the TBSA in China: TBSA (m2) = 0.0061 × height
(cm) + 0.0128 × weight  (kg) − 0.1529. To simplify this com-
plex equation so as to calculate TBSA more easily, we
inquired into a simple formula for estimating TBSA: TBSA 
(m2) = [height  (m) − 0.6] × 1.5.
As listed in Fig. 15.5, the calculated values of the body
surface area in square meters within a specified scope
between the conventional equation (CE) and the simplified
equation (SE) were almost consistent; thus, it was conve-
nient to use the TMMU formula.
As listed in Fig. 15.6 and Tables 15.5 and 15.6, the predic-
tive value changes of the TMMU and the Curreri formulas
were all consistent with REE measured via indirect calorim-
etry (IC), but the TMMU was more precise and unbiased
than the Curreri, as both of the formulas compared with the
REE curve (Fig. 15.6). The mean ratios of EE estimated by
the equation to REE measured via the IC, the TMMU, and
(6)
(6)
(9)
(10) (6)
10
20
30
40
50
60
70
80
90
100 TBSA /%
(6)
(7)
(8)
(8)
(4)
(5)
(5)
PBD 1 ~ 3
PBD 7~28
334.7
(80)
313.8
(75)
292.9
(70)
272.3
(65)
251.0
(60)
230.1
(55)
209.2
(50)
188.3
(45)
(9)
(8)
(6)
(10)
(6)
REE [kJ (Kcal) • m-2 • h-1]
Fig. 15.4  The comparison of REE changes in different burn area
groups between PBD 1–3 and PBD 7–28
1.800
TBSA (m2)
1.700
1.600
1.500
1.400
1.300
1.45 1.50
1.55 1.60 1.65 1.70 1.75 1.80 1.85
Height (m)
Line of CE
Line of SE
1.90
Fig. 15.5  The comparison of the conventional (CE) and simplified
equation (SE) with regard to calculating body surface area
15  Metabolism in Burns

371
the Curreri formulas were higher than 20.5 and 38.4  %
respectively. Although the EEs estimated by the two formu-
las were both lower in minor burns and higher in larger area
burns, the bias of the Curreri was higher than the TMMU
(Tables 15.5 and 15.6). The above comparison data showed
that the administration of the TMMU to estimate energy
requirement in Chinese adult burn victims was more reason-
able than that of the Curreri formula, which has been more
popularly used in China since the 1970s. In 2002, after a
study to evaluate the bias and precision of 46 methods pub-
lished from 1953 to 2000 for estimating EE of thermally
injured patients, Dickerson et  al. concluded that energy
expenditure cannot be precisely predicted; if the IC is not
available, the TMMU formula (1993) is one of the three most
precise and unbiased methods [11].
The REE of 30 healthy adults were measured using the
metabolic cart at the Tianjin Burn Institute, Tianjin the 4th
Hospital, and they found that the REE tallied with the basal
energy expenditure (BEE) calculation using the HB equa-
tion. They also noted that the measured REE was 13  %
higher than the measured BEE, and that the measured BEE
was lower than the BEE calculated using the HB equation in
seven healthy adults [7].
According to the data of the Chinese healthy adult EE
measured with a metabolic cart (CCM; Medical Graphics
Critical Care Monitor Desktop Analysis System) at the
Research Institute of General Surgery, Nanjing General
Hospital, Nanjing Command PLA, the value of REE mea-
sured was about 10 % higher than the BEE measured using
the CCM metabolic cart, and the BEE measured was around
10 % lower than the BEE estimated by the HB equation, i.e.,
the REE measured was roughly equivalent to the BEE esti-
mated using the HB equation in healthy adults [6].
15.1.1.4 The Constituent Ratio of Carbohydrate,
Fat, and Protein in REE Post-burn [4]
It could be seen in Fig. 15.7 that more nitrogen was lost in
large area burns; the peak value of urinary nitrogen was mea-
sured during PBD 7–14. As listed in Table 15.7, and shown
in Figs. 15.8 and 15.9, in the large area burns and/or the ear-
lier phase post-burn, the nonprotein respiratory quotient
(NPRQ) is lower; the NPRQ was higher in minor burns and/
or along with the burn course, i.e. the value of NPRQ post-­
burn was positively correlated with the course of the burn
(Fig. 15.8) and the negative correlation with the increasing
burn area (Fig. 15.9). As the NPRQ value of the ~100 % burn
area group on PBD 1 was only 0.742 ± 0.08, while ~30 % of
the burn area group on PBD 28 reached the high level of
0.905 ± 0.09 (Table 15.7).
The constituent percentage of carbohydrate, fat, and pro-
tein in energy expenditure could be calculated from the REE,
urinary nitrogen and NPRQ, the percentage of these three
nutrients and the consumption ratio of carbohydrate to fat in
non-protein calorie are summarized in Tables 15.8 and 15.9.
5,000
(20,920)
REE
TMMU
1000 (4184)/m2 x TBSA
(m2)+25 (104.6)x TBSAB %
Curreri
25 (104.6)xW (kg)+40 (167.4)
x TBSAB %
4,500
(18,828)
4,000
(16,736)
3,500
(14,644)
3,000
(12,552)
kcal (kJ)/d
5,200
(10460)
2,000
(8,368)
1,500
(6,296)
10
20
30
40
50
60
70
80
90 100 %
TBSAB
Fig. 15.6  Predictive value of energy expenditure (EE) estimated by
Curreri and the Third Military Medical University (TMMU) formula.
TBSAB total body surface area burned
Table 15.5  Comparison of estimating REE kJ kcal
day
(
)
±
(
)
éë
ùû
/
,
x
s
between the Curreri and the Third Military Medical University (TMMU)
formulas
Formula
TBSAB (%)
0–30 (n = 25)
30–50 (n = 15)
50–70 (n = 16)
70–100 (n = 19)
REE
8,230 ± 439
9,669 ± 415
10,799 ± 276
11,355 ± 100
(1,967 ± 105)
(2,311 ± 100)
(2,581 ± 660)
(2,714 ± 240)
TMMU
8,556 ± 1,046
11,171 ± 741
13,263 ± 741
15,898 ± 1,046
(2,045 ± 250)
(2,670 ± 177)
(3,170 ± 177)
(3,795 ± 250)
Curreri
8,125 ± 1,774
12,627 ± 1,289
15,966 ± 1,987
20,071 ± 1,787
(1,942 ± 424)
(3,018 ± 308)
(3,816 ± 475)
(4,797 ± 427)
TBSAB total area of body surface burned
Table 15.6  The ratio of energy expenditure (EE) estimated by equa-
tion to REE measured via indirect calorimetry (IC)
Formula
TBSA (%)
Mean ratio
~30
~50
~70
~100
TMMU
1.040
1.155
1.228
1.398
1.205
Curreri
0.987
1.306
1.478
1.768
1.384
15.1  Hypermetabolism in Burns

372
From the observation of all cases (5–98  % TBSA) in
whole course (PBD 1–28), protein occupied about 15 % in
energy expenditure, the ratio of carbohydrate to fat in non-
protein calories was about 1:1, and the ratio of nonprotein
calories (kcal) to nitrogen (g) is about 150:1. The compari-
son of protein consumption in all cases between PBD 1–3
and PBD 4–28 did not show many changes; the percentage
of carbohydrate consumption clearly decreased in PBD 1–3
and increased significantly during PBD 4–28. The percent-
age of fat consumption in PBD 1–3 is higher and clearly
decreased during PBD 4–28.
If the all cases were divided into two groups (burn area
~50 and 51 %~), throughout the whole burn course (PBD
1–28), the percentage of carbohydrate consumption in the
~50 % group was clearly higher than the 51 %~ group, fat
and protein consumption of 51 %~ group was much higher
than the ~50 % group, i.e., the carbohydrate consumption
was higher in minor burns, and fat and protein consumption
is higher in large area burns. Throughout the whole course
(PBD 1–28) the ratio of carbohydrate to fat in the ~50 %
TBSA group is 1.17:1 and in the ~51 % TBSA group 0.74:1,
nonprotein calories (kcal) to nitrogen (g) in the ~50 % group
was about 180:1, and approximately 126:1  in the ~51  %
group. A comparison of these two groups during PBD 1–3
showed that the percentage of carbohydrate consumption
was higher in the ~50 % group and protein consumption was
higher in the ~51 % group. The difference in fat consumption
between the two groups is not obvious, i.e., the proportion of
carbohydrate consumption was higher in minor and moder-
ate burns and protein consumption was higher in large area
burns during the early phase post-burn. A comparison
between these two burn area groups during PBD 4–28
showed that the percentage of fat consumption in the ~50 %
group was significantly lower than that of the ~51 % group
and there was no obvious difference in carbohydrate and
­protein consumption between the two groups, i.e., the fat
±91
±103
±92
±118
±90
±76
±107
±54
±57
±66
±74
±115
±110
±102
350
300
250
200
150
100
50
TBSAB ≥ 50 %
TBSAB < 50 %
1
2
3
7
14
TBSAB total body surface area burned
21
28 PBD
Urinary nitrogen mmol • d–1
Fig. 15.7  Changes in urinary nitrogen in burns patients
Table 15.7  Nonprotein respiratory quotient (NPRQ) of different time phases in various burns area groups x
s
±
(
)
Burn area
PBD
1
2
3
7
14
21
28
~−0
0.827 ± 0.04
0.832 ± 0.09
0.872 ± 0.06
0.880 ± 0.02
0.899 ± 0.09
0.920 ± 0.05
0.905 ± 0.09
~50
0.799 ± 0.07
0.812 ± 0.06
0.829 ± 0.06
0.856 ± 0.06
0.864 ± 0.02
0.853 ± 0.03
0.889 ± 0.03
~70
0.789 ± 0.03
0.779 ± 0.08
0.819 ± 0.04
0.828 ± 0.06
0.850 ± 0.04
0.843 ± 0.09
0.882 ± 0.04
~100
0.742 ± 0.08
0.735 ± 0.05
0.757 ± 0.06
0.846 ± 0.08
0.820 ± 0.06
0.837 ± 0.04
0.845 ± 0.02
0.925
0.900
0.875
0.850
-NPRQ
0.825
0.800
0.775
1
2
r = 0.847
r = 0.847
p < 0.05
p < 0.05
r = 0.793
r = 0.838
p < 0.05
p < 0.05
a
<30 %
b
c
d
>71 %
31–50 %
51–70 %
3
7
14
21
28 PBD
Fig. 15.8  Positive correlation between nonprotein respiratory quotient
(NPRQ) and burn course
0.925
0.900
0.875
0.850
NPRQ
0.825
0.800
0.775
0.750
10
20
30
40
50
60
70
80
90
100TBSAB %
r = –0.958
p < 0.01
r = –0.760
p < 0.05
r = –0.975
p < 0.01
PBD28
PBD7
PBD1
a
b
c
Fig. 15.9  Negative correlation between NPRQ and increasing burn
area
15  Metabolism in Burns

373
consumption of minor and moderate burns clearly decreased
during the later phase of the burn course.
As is known to all, the lack of carbohydrate and protein
was not permitted and excessive supplementation can be
detrimental. From analyzing nutrient consumption of burns
patients in this group measured by the TMMU, if the protein
supplement constitutes 15 % of the total energy expenditure
(TEE), the ratio of carbohydrate to fat in nonprotein calories
was about 1:1 (0.93:1), i.e., both of them occupied about
40  % of TEE respectively. During the early stage (PBD
1–3), the ratio of carbohydrate to fat was about 3:5 (0.63:1,
i.e., carbohydrate consumption accounts for about 30 % of
TEE, while fat about 50 % of TEE); after PBD 4, the pro-
portion of carbohydrate to fat is about 5:4 (1.25:1, i.e. car-
bohydrate occupies about 50 % of TEE, and fat about 35 %).
In the burn area <50 % group, the proportion of carbohy-
drate to fat is about 1.2:1 (PBD 1–28), about 0.76:1 in the
early stage (PBD 1–3), about 1.6:1 on PBD 4–28; in the
burn area >50 % group, the proportion of carbohydrate to fat
was 0.74:1, by PBD 1–3 about 0.5:1, and 0.96:1 on PBD
4–28. This still needs further testing and verifying whether
the consumption ratio of carbohydrate to fat is fully suitable
for the supplemental proportion of carbohydrate to fat in
burn adults.
The above-mentioned paragraphs only comprise our pre-
liminary study of EE in burns patients. Two points in these
data, the results and conclusions, should be explained:
1. These data and conclusions were all obtained under our
routine meals for burn patients; these may be changed if a
different style of meal is substituted.
2. The nitrogen output calculated only included urinary
nitrogen and not wound nitrogen Although there are
many methods of calculating nitrogen loss from burn
wound, and they are only by rough estimation. In cal-
culating REE and NPRQ, we did not add loss of wound
nitrogen to the total loss of nitrogen. The loss of
wound nitrogen did not enter into oxidation and
metabolism, and calculating the percentage of protein
consumption in NPRQ and REE was not affected by
the loss of some of the wound nitrogen. However, this
part of protein and other nutrients lost from burn
wound should not be left out while estimating the sup-
plementation of protein and others. Therefore, it is
still a problem of experimental burn surgery that needs
to be solved, i.e., how to calculate the loss of protein
and other nutrients from burns wounds.
15.1.2
“Enterogenous Hypermetabolism”
After Burn Injury [1–3, 12, 13]
“Enterogenous hypermetabolism (EH)” was put forward
in1996, and is still being further investigated nearly 20 years
later. We believe there EH exists after burn injury and the
main points are as follows.
15.1.2.1 The Origin and Significance of EH
The hypermetabolism originates not only in the burn wound,
but also from the internal organs, especially the intestine.
The intestinal ischemia and anoxia induced by covert com-
pensated shock during the early phase of severe burns form
the basis of post-burn EH. Further study is needed to dis-
cover whether it is possible to initiate internal hypermetabo-
lism from other viscous injuries induced by covert
compensated shock. Since the mid-1980s, about 700 animals
(576 rats, [250 ± 30] g; 60 rabbits, [2.0 ± 0.5] kg; 60 mini-­
pigs, [22 ± 2.5] kg) and 200 burns patients including 40
severe cases with TBSA 45± 11.3  % and deep burn
29.7 ± 10.4 % were investigated. After this serial study last-
ing more than 20 years, we believe that the EH is present
after burn injury. If the EH truly exists, it is beneficial to the
recovery of the burn organism by modulating and
decreasing.
15.1.2.2 Intestine Injury After Severe Burns
Under the conventional fluid resuscitation, intestinal isch-
emia and anoxia evidently exist.
Table 15.8  The percentages of carbohydrate, fat, and protein in REE
x
s
±
(
)
Burns area PBD
Carbohydrate (%)
Fat (%)
Protein (%)
5–50 %
(n = 33)
1–3
38.3 ± 7.8*
50.1 ± 6.5
11.3 ± 1.0**
4–28
54.0 ± 7.9
33.1 ± 7.3**
12.8 ± 2.6
1–28
47.3 ± 11.1**
40.4 ± 11.0*
12.2 ± 2.4**
51–98 %
(n = 26)
1–3
27.8 ± 4.2
54.2 ± 5.2
18.0 ± 3.8
4–28
41.4 ± 6.3
43.1 ± 4.5
15.5 ± 3.6
1–28
35.6 ± 8.8
47.8 ± 7.4
16.6 ± 3.7
5–98 %
(n = 59)
1–3
33.0 ± 8.1***
52.5 ± 6.5***
14.7 ± 6.5
4–28
47.7 ± 9.5
38.1 ± 7.8
14.2 ± 3.3
1–28
41.4 ± 11.5
44.1 ± 10.0
14.4 ± 4.1
5–50 % vs 51–98 % group:*p < 0.05, **p < 0.01; 1–3 vs 4–28 PBD in
5–98 % group:***p < 0.05
Table 15.9  The proportion of carbohydrate to fat consumption in non-
protein calories
Burn area
PBD
Proportion of carbohydrate to fat consumption
5–50 %
(n = 33)
1–3
0.76:1
4–28
1.63:1
1–28
1.17:1
51–98 %
(n = 26)
1–3
0.51:1
4–28
0.96:1
1–28
0.74:1
5– % (n = 59)
1–3
0.63:1
4–28
1.25:1
1–28
0.94:1
15.1  Hypermetabolism in Burns

374
1. The intestine and portal blood flow are decreased
post-burn
After using the Parkland formula for fluid resuscita-
tion, the portal blood flow of 30  % of the TBSA
­third-­degree burn of mini-pigs (Gui-Zhou species) was
clearly reduced (Table 15.10). The intestinal blood flow
of 30 % of the TBSA third-degree burn in the rat was also
significantly reduced after using intraperitoneal injection
of balanced salt solution (50 ml/kg) immediately after the
burn (Table 15.11).
2. The energy reservoir of intestinal mucosa cell is declined
The oxygen uptake rate (OUR) of intestinal tissue [OU
R, (Sa*O2 × Hba* − Sv▲O2 × Hbv▲)/(Sa*O2 × Hba*), *a : 
artery, ▲v : vein], the energy charge of gut mucosa
[EC, (ATP + 1/2ADP)/(ATP + ADP + AMP)], the respi-
ratory control rate (RCR, ST3/ST4), and ratio of phospho-
rus to oxygen (P/O) of enterocyte mitochondria were all
decreased (Table 15.12).
3. Suppression of intestinal mucosa proliferation and
reparation
The 3H-thymidine incorporation rate (3HTIR), the
3H-uridine incorporation rate (3HUIR), the 3H-leucine
incorporation rate (3HLIR), the proliferation index (PI,
S+G2+M), the proliferating cell nuclear antigen (PCNA),
the intestinal trefoil factor (ITF), and the insulin-like
growth factor II (IGF-II) of the intestinal mucosa were all
decreased, but the TGF-β1 was increased (Table 15.13).
4. The structure and function of the intestine were damaged
The mucus layer depth (MLD) and its content of pro-
tein, hexose, and SIgA decreased. Intestinal mucosa
thickness (MT), villus height (VH), villus surface area
(VSA), crypt depth, and activity of Na+-K+-ATPase were
all reduced. The ratio of urine lactulose to mannitol
(L/M), the plasma activity of diamine oxidase (DAO),
mitochondrion malondialdehyde (mMDA) and intracel-
lular Ca2+ (Ca2+i) of the intestinal mucosa cell were all
increased. Intestinal absorption (IA) of glucose, fat and
amino acid, and intestinal transit (IT, the percentage of
carbon staining the whole intestine mucosa) decreased
(Tables 15.14, 15.15, and 15.16).
15.1.2.3 Hypermatabolism and Intestine
Injury [14–18]
Inflammatory mediators secreted by intestine mucosa and
the level of portal endotoxin induced by intestine injury
were increased and both correlated significantly with
REE.
1. Inflammatory mediators secreted by the gut mucosa
increased, and had a significantly positive correlation
with REE. Gut mucosa TNF, IL-1, IL-6, PGE2 in 30 %
of the TBSA third-degree burn rats were all clearly
increased. REEs of PBD1, 3, 5 correlated significantly
with intestinal mucosa TNF (r =0.8113, p < 0.05), IL-1
(r =0.5797, p < 0.05), IL-6 (r =0.9137, p < 0.05;
Table 15.17).
PBD 1–14 REEs positively correlated with plasma
TNF, MDA, glucagon, cortisol, and urine catecholamine
in adults with burns covering 45 % of the TBSA, the cor-
relation coefficients were 0.9622 (p < 0.01), 0.9124
(p < 0.01), 0.9502 (p < 0.01), 0.8229 (p < 0.05), 0.9519
(p < 0.01) respectively.
Table 15.10  Changes in portal blood flow in third-degree burns cover-
ing 30 % of the TBSA in mini-swine ml/kg·min, x
s n
±
=
(
)
,
6
Pre-burn
PBH 6
PBD 4
PBD 7
PBD 10
25.7 ± 6.1
6.4 ± 2.8*
8.8 ± 3.0*
17.3 ± 3.1
16.4 ± 3.3
100 %
24.9 %
34.2 %
67.3 %
63.8 %
PBH post-burn hour; vs pre-burn *p < 0.01
Table 15.11  Changes in intestinal blood flow in rats with third-degree burns covering 30 % of the TBSA mv,
,
x
s n
±
=
(
)
8
Pre-burn
PBD 1
PBD 2
PBD 3
PBD 5
PBD 7
139.9 ± 8.3
67.8 ± 2.5*
92.0 ± 8.5*
90.1 ± 6.1*
102.3 ± 9.7*
91.1 ± 36.2*
100 %
48.4 %
65.8 %
64.4 %
73.1 %
65.1 %
vs pre-burn * p < 0.01
Table 15.12  Changes in the energy reservoir of intestinal mucosa cells in rats with third-degree burns covering 30 % of the TBSA x
s
±
(
)
Normal
PBH 6
PBH 24
PBD 3
PBD 7
PBD 10
OUR (n = 8)
0.3475 ± 0.0303
0.2159 ± 0.0188*
0.1486 ± 0.0179*
0.2337 ± 0.0288*
0.3133 ± 0.0198**
0.2467 ± 0.0237*
100 %
62.1 %
42.8 %
67.3 %
89.6 %
71.0 %
EC (n = 6)
0.838 ± 0.018
0.625 ± 0.036*
0.553 ± 0.036*
0.584 ± 0.044*
0.650 ± 0.049*
0.595 ± 0.042*
100 %
74.6 %
66.0 %
69.7 %
77.6 %
71.0 %
RCR (n = 6)
4.21 ± 0.29
3.02 ± 0.17*
2.88 ± 0.13*
3.29 ± 0.21*
3.43 ± 0.24*
2.77 ± 0.20*
100 %
71.7 %
68.4 %
78.1 %
81.5 %
65.8 %
P/O (n = 6)
2.52 ± 0.22
1.88 ± 0.22*
1.83 ± 0.14*
1.91 ± 0.17*
2.18 ± 0.19**
1.79 ± 0.12*
100 %
74.6 %
72.6 %
75.8 %
86.5 %
71.0 %
vs normal *p < 0.01, **p < 0.05
15  Metabolism in Burns

375
Table 15.13  Suppression of changes in intestine mucosa proliferation and reparation in rats with third-degree burns covering 30 % of the TBSA x
s n
±
=
(
)
,
6
Normal
PBH 6
PBH 12
PBD 1
PBD 2
PBD 3
PBD 5
PBD 7
PBD 10
3HTIR (dpm/cm)
3,138 ± 268
2,535 ± 231*
1,968 ± 269*
2,208 ± 255*
2,423 ± 262*
1,984 ± 221*
100 %
80.8 %
62.7 %
70.4 %
77.2 %
63.2 %
3HUIR (dpm/cm)
2,235 ± 247
1,272 ± 253*
1,849 ± 227**
100 %
56.9 %
82.7 %
PI (%)
60.1 ± 6.8
38.6 ± 15.3**
35.1 ± 12.6*
40.2 ± 13.0*
42.3 ± 6.8*
45.2 ± 20.7
100 %
64.2 %
58.3 %
66.8 %
70.3 %
75.1 %
PCNA (OD)
823.5 ± 240.6
766.5 ± 189.7
466.6 ± 171.3**
307.3 ± 154.9*
247.4 ± 112.2*
311.5 ± 132.4*
100 %
93.1 %
56.7 %
37.3 %
30.0 %
37.8 %
ITF (ng/g pro#)
369.3 ± 65.6
588.2 ± 100.3**
343.7 ± 51.8
127.7 ± 45.5*
98.7 ± 40.3 %*
15.8 ± 4.4*
100 %
159.3 %
93.1 %
34.6 %
26.7 %
4.3 %
IGF-II (pg/mg pro#)
594.2 ± 103.9
357.4 ± 228
388.1 ± 130.4**
359.5 ± 96.3**
351.9 ± 79.3**
433.3 ± 263.6
100 %
60.1 %
65.3 %
60.5 %
59.2 %
72.9 %
TGF-β1 (pg/mg pro#)
93.9 ± 14.7
170.7 ± 18.6*
143.1 ± 14.9*
285.9 ± 95.3**
134.1 ± 38.2
631.3 ± 56.1*
100 %
181.8 %
152.4 %
304.5 %
142.8 %
672.3 %
pro# protein vs normal; *p < 0.01; **p < 0.05
Table 15.14  Change of intestinal structure and function in rats with third-degree burns covering 30 % of the TBSA x
s
±
(
)
Normal
PBH 6
PBH 12
PBD 1
PBD 2
PBD 3
PBD 5
PBD 7
PBD 10
MLD (mg, n = 8)
7.84 ± 0.72
8.62 ± 0.26**
7.20 ± 0.44*
6.85 ± 0.63*
6.26 ± 0.34*
5.02 ± 1.33*
100 %
109.9 %
91.8 %
87.4 %
79.8 %
64 %
MT (μm, n = 6)
618 ± 69.7
325.1 ± 22.5*
368.3 ± 57.4*
445.4 ± 40.7*
375.0 ± 50.3*
226.9 ± 24.9*
100 %
52.6 %
59.6 %
72.1 %
60.7 %
36.7 %
VH (μm, n = 8)
456 ± 58.5
225.6 ± 21.3*
257.3 ± 41.6*
314.6 ± 34.9*
248.7 ± 32.3*
145.7 ± 14.4*
100 %
49.5 %
56.4 %
69.0 %
54.5 %
32 %
VSA (mm2 × 103, n = 6)
119 ± 18
41 ± 10*
49 ± 11*
65 ± 9*
47 ± 9*
24 ± 6*
100 %
34.5 %
41.2 %
54.6 %
39.5 %
20.2 %
DAO (U/ml, n = 8)
0.32 ± 0.02
1.23 ± 0.53*
1.05 ± 0.31*
0.88 ± 0.21*
0.60 ± 0.14*
0.70 ± 0.16*
100 %
384.4 %
328.1 %
275 %
187.5 %
218.8 %
Ca2+i (nmol/L, n = 6)
207.8 ± 20
389.7 ± 25.4*
411.0 ± 16.4*
323.4 ± 31.7*
270.2 ± 27.5*
355.5 ± 58.5*
100 %
187.5 %
197.8 %
155.6 %
130 %
171.1 %
mMDA (nmol/g pro, n = 6)
577 ± 71
932 ± 165*
1,042 ± 177*
905 ± 96*
743 ± 108**
803 ± 112**
100 %
161.1 %
180.6 %
156.8 %
128.8 %
139.2 %
IT (%, n = 6)
62.0 ± 6.8
12.0 ± 3.3*
12.5 ± 3.3*
22.9 ± 5.9*
25.0 ± 7.3*
34.1 ± 3.9*
100 %
19.4 %
20.1 %
36.9 %
40.2 %
54.9 %
Pro protein, MLD mucus layer depth, MT mucosa thickness, VH villus height, VSA villus surface area, DAO diamine oxidase, mMDA mitochondrion malondialdehyde, IT intestinal transit; vs
normal *p < 0.01; **p < 0.05
15.1  Hypermetabolism in Burns

376
2. The level of plasma endotoxin in the portal vein was sig-
nificantly higher than in the central vein; plasma endo-
toxin was clearly correlated with REE.
(a) The levels of plasma endotoxin in the portal vein
of 30  % of the TBSA third-degree burns in mini-
pigs on post-burn hour (PBH) 4, 6, 24, 48, and
72 were 591.3 ± 28.4, 928.7 ± 40.7, 975.7 ± 48.3,
543.5 ± 41.4, 591.8 ± 19.8  EU/L respectively. The
levels of plasma endotoxin in the central vein were
396.8 ± 124.6, 434.0 ± 120.1, 639.3 ± 30.6, 401.5 ± 26.6,
513.0 ± 65.5 EU/L respectively. The levels of plasma
endotoxin in the portal vein were clearly higher than
in those in the central vein 49.0 %, 113.9 %, 52.5 %,
35.4 %, 15.4 % separately (all p < 0.05–0.01).
(b) PBD 1–14 REEs correlated significantly with plasma
endotoxin in adults with burns covering 45 % of the
TBSA (r =0.5985, p = 0.014; Table 15.18).
(c) Induction of hypermetabolism in guinea pigs by
endotoxin infused through the portal vein [19].
15.1.2.4 Early Feeding (EF) Can Alleviate
Intestine Injury and Reduce
Hypermetabolism
1. Intestinal injury reduced by early feeding
After burn injury, early feeding (EF) can resuscitate
the gut, improve the blood flow of the portal vein and
intestinal mucosa, and alleviate gut ischemia and reperfu-
sion injury. EF can improve the energy reservoir of the
intestinal mucosa, lessening the decrease in the OUR,
epithelial cells (ECs), RCR, and P/O. EF can mitigate the
suppression of intestinal mucosa proliferation and repara-
tion, reduce the decrease in 3HTIR, 3HUIR, 3HLIR, PI,
PCNA, ITF, and IGF-II of the intestinal mucosa. EF could
preserve the structure and function of the intestine, reduce
the decrease in intestinal MLD, MT, VH, and VSA, lower
the increasing range of DAO, L/M and Ca2+i, and improve
the function of IA and IT.
2. EF decreased the level of plasma endotoxin and inflam-
matory mediators
EF was able to decrease the level of plasma endotoxin,
TNF, and IL-8 in adults with burns covering 45±11.3 %
of the TBSA and mini-pigs with 30 % of the TBSA third-
degree burn (Tables 15.19, 15.20, and 15.21).
During PBD 1–14, the average value of urinary nitrogen
of adults with burns covering 45 % of the TBSA in the EF
group was 20.4 ± 4.2  g/day and in the DF group it was
25.8 ± 5.4 g/day; the EF was lower (5.4 ± 1.2 g/day) than in
the DF group (p < 0.02), and the p value of PBD 7, 9, 10, 12,
13, and 14 in the EF and DF groups are all <0.05–0.01 (Table
15.22).
15.1.2.5 Mechanism and Modulation of EH
The mechanism and modulation of EH are demonstrated in
(Figs. 15.10 and 15.11)
Table 15.15  Changes in intestinal absorption function in mini-pigs
with third-degree burns covering 30 % of the TBSA x
s n
±
=
(
)
,
6
Absorption
Pre-burn
PBD 4
PBD 7
PBD 10
Glucose
(μmol/kg·min)
134.3 ± 33.2 48.3 ± 16.4* 103.0 ± 19.8 94.8 ± 18.9**
100 %
36 %
76.7 %
70.6 %
Fat
(mg/kg·min)
38.7 ± 8.0
13.9 ± 5.3*
33.5 ± 5.6
28.8 ± 7.5
100 %
36 %
86.5 %
74.7 %
Amino acid
(μmol/kg·min)
77.0 ± 21.5
16.3 ± 6.2*
61.1 ± 17.4
100 %
21.1 %
79.3 %
vs pre-burn *p < 0.01; **p < 0.05
Table 15.16  Changes in serum DAO and urine L/M in adults with
burns (46.5 ± 8.4 % of the TBSA, deep burn 29 ± 14 %, x
s n
±
=
,
9)
PBD
1
4
8
14
Serum DAO
(U/ml)
3.57 ± 1.21
3.43 ± 0.59
2.57 ± 0.79
2.26 ± 0.90**
Urine L/M
0.19 ± 0.04
0.27 ± 0.04*
0.21 ± 0.03
0.18 ± 0.05
It is impossible to measure the pre-burn value of burn patients. There
are many different values of serum DAO and urine L/M in normal
adults or trauma patients among journals, for example:
1. Normal or patient value of serum DAO: (a) Normal value: 0.12 ± 0.06,
Chinese J Emerg, 2006, 26(12):89]; (b) normal value: 0.312 ± 0.009,
Medical College Journal of North Chinese Coal, 2007, 9(3):292; (c)
patient with abdominal operation: 1.25–3.18, Parenteral and Enteral
Nutrition, 2002, 9:72.
2. Normal or patient value of urine L/M: (a) Normal value: 0.043 ± 0.06,
abdominal disease: 0.158 ± 0.040, Gut, 1993, 34(3):354; (b) normal
value: 0.015 ± 0.01, trauma patient: 0.055–1.650, Crit Care Med, 1995,
23(4):660; (c) normal value: 0.02 ± 0.01, Clin Exp Rheumatol,
2000,18(6):773; (d) normal value: 0.033 ± 0.004, Chinese J of Infection
Disease, 2002, 20(2):106; (e) trauma patient: 0.088 ± 0.311, JPEN, 2007,
31(2):119; (f) normal value: 0.021 ± 0.0016, Peking Union Hospital.
The values of two indexes in our burns patient are much higher than the
normal and some of the disease values.
vs PBD1 *p < 0.01, **p < 0.05
L/M lactose to mannitol
Table 15.17  Changes in intestinal mucosa TNF (ng/mg protein), IL-1 (ng/mg protein), IL-6 (pg/mg protein), PGE2 (pg/mg protein), and REE
(kJ/m2·d) x
s n
±
=
(
)
,
5
Normal
PBD 1
PBD 3
PBD 5
PBD 7
TNF
1.71 ± 1.00
5.94 ± 1.90*
4.77 ± 2.98
2.94 ± 0.91
2.36 ± 0.68
IL-1
3.36 ± 0.93
13.54 ± 4.28*
3.50 ± 1.30
3.28 ± 0.82
3.43 ± 1.28
IL-6
1.42 ± 1.42
4.68 ± 1.50*
2.55 ± 0.55
3.13 ± 0.89*
2.75 ± 0.45
PGE2
8.05 ± 0.61
18.85 ± 2.46*
7.04 ± 1.94
6.56 ± 0.61
7.84 ± 1.11
REE
4,673 ± 1,941
8,537 ± 2,676*
7,272 ± 515
7,814 ± 2,853
12,113 ± 2,643*
vs normal *p < 0.05
15  Metabolism in Burns

377
Table 15.18  Changes in PBD 1–14 REEs and plasma endotoxin in adults with a burn covering 45 % of the TBSA x
s n
±
=
(
)
,
40
PBD
1
4
8
14
REE(kJ/
day)
7,591 ± 850 7,560 ± 778 7,682 ± 781 7,364 ± 661 7,933 ± 1,258 8,270 ± 753 9,447 ± 956 9,720 ± 1,519 8,541 ± 1,459 9,225 ± 934 10,817 ± 941 10,444 ± 1,059 9,568 ± 1,438 10,012 ± 831 11,092 ± 1,157 11,081 ± 1,589
Endotoxin
(EU/L)
308 ± 63
320 ± 76
330 ± 74
321 ± 101
546 ± 118
652 ± 135
853 ± 103
756 ± 113
495 ± 150
530 ± 205
780 ± 145
754 ± 130
449 ± 133
438 ± 119
555 ± 199
533 ± 164
Table 15.19  Changes in plasma endotoxin in the portal vein of mini-pigs with third-degree burn covering 30 % of the TBSA EU L
/
,
,
x
s n
±
=
(
)
6
Pre-burn
PBH 4
PBH 6
PBH 12
PBD 1
PBD 2
PBD 3
PBD 4
PBD 5
PBD 7
PBD 10
EF
257.0 ± 28.7
420.2* ± 44.7
455.7* ± 20.2
231.8* ± 27.9
475.3* ± 24.1
279.0* ± 19.0
365.5* ± 15.4
260.0* ± 9.8
275.8** ± 27.1
266.5** ± 14.5
329.0 ± 16.7
DF
230.2 ± 23.5
591.3 ± 28.4
928.7 ± 40.7
436.0 ± 52.1
975.7 ± 48.3
543.5 ± 41.4
591.8 ± 19.8
637.2 ± 27.7
356.8 ± 22.9
318.7 ± 19.9
399.8 ± 13.5
EF enteral feeding group, DF delayed feeding group; vs DF *p < 0.01; **p < 0.05
Table 15.20  Changes in plasma endotoxin in adults with burns covering 45 % of the TBSA EU L
/
, x
s
±
(
)
PBD
1
4
8
14
EF (n = 11)
308 ± 63
546 ± 118**
495 ± 150**
449 ± 133
DF (n = 10)
321 ± 101
756 ± 113
754 ± 130
533 ± 164
EF lowers hypermetabolism
vs DF **p < 0.01
Table 15.21  Changes in REE in adults with burns covering 45 % of the TBSA kcal m
h
·
·
,
-
-
±
(
)
2
1 x
s
PBD
Normal (n = 8)
PBD 1
PBD 4
PBD 8
PBD 14
EF (n = 11)
38.4 ± 3.9
47.8 ± 5.4
50.0 ± 7.9*
53.8 ± 9.2**
60.3 ± 9.1**
DF (n = 10)
47.0 ± 4.2
62.1 ± 9.7
66.7 ± 6.8
70.7 ± 10.1
vs DF *p < 0.05, **p < 0.01
Table 15.22  Changes in urinary nitrogen in adults with burns covering 45±11.3 % of the TBSA g day
/
,x
s
±
(
)
PBD
1
2
3
4
5
6
7
8
9
10
11
12
13
14
EF (n = 11)
12.8 ± 2.6
13.1 ± 4.2
16.4 ± 5.8
18.9 ± 7.7
21.5 ± 9.3
25.0 ± 7.8
25.2* ± 9.1
25.5 ± 9.4
20.2** ± 7.4
18.2** ± 4.4
22.6 ± 8.8
22.5** ± 7.2
23.9** ± 6.9
20.4** ± 6.6
DF (n = 10)
13.1 ± 4.2
16.1 ± 6.3
21.7 ± 6.6
22.0 ± 5.6
24.4 ± 6.8
28.7 ± 5.5
30.2 ± 6.3
31.0 ± 6.9
25.2 ± 9.3
28.4 ± 8.3
28.5 ± 6.1
28.8 ± 6.7
30.2 ± 4.9
33.5 ± 9.2
vs DF *p < 0.05, **p < 0.01
15.1  Hypermetabolism in Burns

378
Severe burn
Intestine injury of ischemia & anoxia
Obstacle of energy
metabolism in intestine
Suppression of intestine mucosa
proliferation & reparation
Injury of intestine
structure & function
Intestine mucosa activation
release inflammatory mediators
Translocation of intestine endotoxin
portal endotoxin increased
EH
(REE ↑ )
Fig. 15.10  Mechanism of
enterogenous hypermetabolism
(EH)
EF, Gln, Immunonutrition,etc
Promote intestine
resuscitation
Reduce Intestine Injury
Improve energy metabolism
of intestine mucosa
Lessen depression of mucosa
proliferation & reparation
Maintain intestine
structure & function
Modulate intestine mucosa, decrease
secretion of inflammtory mediators
Decrease translocation of endotoxin
lower portal endotoxin
Modulate EH
(REE )
Ę
Fig. 15.11  Modulation of EH
15  Metabolism in Burns

379
15.2
Glycometabolism
Zhanke Wang and Linshui Xu
The research contents of burn glycometabolism include as
follows:
1. The dynamic change of glycometabolism in a variety of
in vivo and in vitro tissue cells.
2. Clarifying the mechanism of post-burn glycometabolism
disorder and insulin resistance at the level of insulin
receptor and signal transduction.
3. Researching the characteristics and hazards of burn
hyperglycemia, proposing the program and formula of
individualized glucose–insulin–potassium (GIK) therapy,
and implementing treatment for severe burns with glyco-
metabolism disorder.
15.2.1
Explore the Performance of Post-
burn Glycometabolism Disorder
[20–31]
15.2.1.1 The Types of Post-burn Hyperglycemia
Post-burn hyperglycemia can be classified into transient
hyperglycemia and persistent hyperglycemia according to
the increasing duration of the patient’s glycemia. Based on
the stage, post-burn hyperglycemia can be classified into pri-
mary hyperglycemia and secondary hyperglycemia. Based
on the degree of increasing glycemia, post-burn hyperglyce-
mia can be classified into mild hyperglycemia (5.8–
8.0 mmol/L), moderate hyperglycemia (<11.0 mmol/L), and
severe hyperglycemia (<15.0 mmol/L).
A large number of clinical data in our country have indicated
that there may be transient hyperglycemia post-burn. Generally,
it rises rapidly and falls to a normal level after 2 h. Fasting
blood-glucose is usually less than 8.0  mmol/L, and insulin
treatment is not necessary if typical clinical symptoms of diabe-
tes do not appear; however, the dynamic change in glycemia
should be observed closely. The patient is likely to develop per-
sistent hyperglycemia if there is accompanying infection and
multi-organ dysfunction syndrome (MODS). Therefore, atten-
tion to drawn to clinical observation when the post-burn fasting
blood glucose concentration is above 8.0 mmol/L.
Primary persistent hyperglycemia mainly occurs in
patients with particularly severe burns, which are character-
ized by their severe consequences and poor prognosis; thus,
early diagnosis and treatment are necessary. In some patients
with severe burns, hyperglycemia does not occur or fall backs
to normal until hyperglycemia has lasted 2 days, and then
persistent hyperglycemia occurs again a week later. This phe-
nomenon is called secondary persistent hyperglycemia.
Secondary persistent hyperglycemia is related to post-­burn
accompanying infections and MODS, and is the expression
of the deterioration of burns patients after the shock period;
usually, it can be taken as an indicating index for MODS.
15.2.1.2 Explore the Post-burn Disorder
of Glucose Uptake
On the one hand, non-insulin-dependent glucose uptake (as
in hemocytes, especially in an inflamed granulocyte system)
is enhanced; on the other hand, insulin-dependent glucose
uptake disorder (mostly in myocytes) becomes more obvi-
ous. We have taken rats with third-degree burns covering 30
or 37 % of the TBSA as models, using 3H-2-DG as a tracer to
research the dynamic alteration in glucose uptake of in vivo
and in vitro liver tissue, muscle tissue, and fat tissue. Results
showed that regardless of in vivo or in vitro soleus of severe
burned rats, the uptake of 3H-2-DG (deoxyglucose) in lipo-
cytes shows no significant difference from the normal con-
trol group when no irritation of insulin influences the glucose
uptake (i.e., basic uptake). However, the glucose uptake of
some other tissues, such as the liver of burned rats, rapidly
decreases with the irritation of insulin and the accompany-
ing obvious insulin resistance. It is noteworthy that infection
and inflammation often occur in skeletal muscle, thus causing
mononuclear phagocyte and mechanocyte infiltration regard-
less of whether the burn is in vivo or in vitro, the glucose
uptake of the injured limb is three to six times higher than in
the uninjured limb, even more than the glucose uptake in liver,
spleen, lung, ileum, and skin, which are abundant in mononu-
clear phagocyte increases because of infection. Meanwhile, the
systemic glucose consumption also increases. The research of
the Burn Research Institute, Chongqing Southwest Hospital,
proved that GluT-1 mRNA expression obviously increased
in liver tissue of severely burned rats. However, our research
showed that the total amount of GluT-4 in skeletal muscle of
severely burned rats was unchanged, but the transferability of
GluT-4 to epicytes irritated by insulin decreased. It is shown
that burn inflammatory infiltration is the main cause leading
to the increase in glucose uptake and consumption. By non-
insulin dependence mononuclear phagocytes take up a large
amount of glucose and strengthens the pentose phosphate
metabolizing pathway, then produces more nicotinamide ade-
nine dinucleotide phosphate (NADPH) to maintain the intra-
cellular concentration of glutathione (GSH), and generates
H2O2, O2
• to participate in a respiratory burst.
15.2.1.3 Explore Post-burn Reduction
of Glucose Utilization
Zhongjin Tang et  al. in the Second Military Medical
University, Shanghai, used the euglycemic insulin clamp
technique to research the glucose removal rate (M) of rats
with third-degree burn injuries covering 20 % of the TBSA,
the result showed that it clearly decreased compared with the
normal control group. At that moment only part of the input
glucose was oxidized to CO2 by the burn-injured organism.
15.2  Glycometabolism

380
Most of the glucose was transformed to lactic acid and then
by the way of gluconeogenesis to the carbon cycle. In the
research into uptake and utilization of 2-DG (deoxyglucose)
in in vitro skeletal muscle (musculus soleus) of scalded rats,
we found that the basic glucose ingestion of the scalded
group showed no significant difference from the normal con-
trol group; however, the 2-DG-6 phosphoric acid content
was clearly higher than in the normal control group. This fact
showed that although the utilization of glucose in burn-­
injured myocytes could phosphorylate glucose, further oxi-
dization and utilization were distinctly limited.
15.2.1.4 Explore Post-burn Production Increase
in Glucose
The Department of Biochemistry, at the Third Military
Medical University, Chongqing, studied the carbohydrate
metabolism alteration of rats with napalm third-degree burn
covering 30 % of the TBSA. The result was that the hepatic
glycogen content in burn-injured rats decreased immediately,
was almost exhausted after 1 day, then slightly recovered after
3–5  days; however, a tendency to decline appeared 7  days
later. The phenomenon indicated that post-burn hepatic glyco-
gen broke down rapidly. After that, the activity of G-6-
phosphatase, pyruvate carboxylase, and phosphoenolpyruvate
carboxykinase (PEPCK) was observed, which are the three
key enzymes for gluconeogenesis in the liver and kidney. The
result proved that the activity of the three key enzymes for
gluconeogenesis in liver and kidney strengthened sharply,
especially that of PEPCK. The kidney still has a significant
effect on post-burn gluconeogenesis. The above-mentioned
research result was in accordance with the result of the early
report by Allsop, etc., that stated that the post-burn ­endogenous
glucose production of patients with burn injuries ­covering
20 % of the TBSA was obviously higher than in the normal
control group on PBD 1–7. Post-­burn gluconeogenesis
strengthening was partly the result of a large amount of post-
burn secretion of glycotropic hormone, partly because insulin
resistance declined the ability to suppress gluconeogenesis.
Meanwhile, post-burn hypermetabolism reaction, a large
amount of tissue protein decomposition, the strengthening of
lipid mobilization and hyperlactatemia provided the material
for gluconeogenesis. It is worth emphasizing that the post-
burn insulin/glucagon (I/G) ratio reduction plays a vital role in
the post-burn strengthening of gluconeogenesis.
15.2.2
Explore the Mechanism of Post-burn
Glycometabolism Disorder [32–42]
15.2.2.1 Clarify Post-burn Insulin Receptor
Signal Disorder
1. In the early stages of severe burn-injury, the organism had
hyperglycemia and hyperinsulinemia reactions. Non-
insulin-­dependent glucose uptake in the liver or other
internal organs increased, and the change in insulin-­
dependent intra-cellular phosphorylation of glucose was
less obvious. The reaction of muscle (soleus) to insulin
stimulated by 2-deoxyglucose uptake, whether in vivo or
in vitro, was clearly disordered. The post-injured insulin
resistance may be seen on the injured part (tissue), and
also on the non-injured parts (tissue) of the injured body,
which could continue from the shock phase to hyperme-
tabolism. Moreover, the contents of cAMP and free fatty
acids (FFA) in lipocytes did not noticeably alter. The
result showed that severe post-burn insulin resistance
mainly led to the strengthening of the intra-cellular sub-
strate cycle and energy exhaustion.
2. In the early stages of a severe burn, the test combined the
insulin receptors of erythrocytes, hepatocytes, lipocytes,
and muscular cell plasmalemma. The insulin receptor
binding test in the liver and muscle, partly purified by
sepharose 4B-WGA affinity chromatography, showed
that the Bmax maximum binding capacity) obviously
decreased. However, the B/Tmax (maximum binding rate)
altered less and the average affinity of the receptor (espe-
cially low affinity) increased.
3. In the early stages of a severe burn (PBD 3–5) the activity
increase in adenine nucleotide cyclase (Ac) stimulated by
glucagon and adrenaline on the epicyte of the liver and
muscle was evidently lower than in the normal control
group, and the activity of Ac, which was stimulated by
various doses of insulin, could be suppressed. The suppres-
sion stimulated by a megadose (32 nmol/L) of insulin had
no significant difference from that in the normal control
group, but suppression of the burn-injured group stimu-
lated by a low dosage of insulin was significantly lower
than in the normal control group. The isodose curve of
­suppression shifted to the right, and the ED50 (median
effective dose) increased. The result showed that the sensi-
tivity of the suppression effect of insulin on Ac of the liver
and muscle cells after severe burns was decreased, while
the maximal responsivity was normal, which suggested
that the coupling of post-burn insulin receptor–adenylate
cyclase signal transduction access might have a defect.
Equally, low Km (Michaelis constant) cAMP-PDE (phos-
phodiesterase) activity on the lipocytes of burn-­injured rats
was lower than in the normal control group. Insulin could
stimulate the cAMP-PDE activity of adipose tissue on
uninjured and injured rats and the activity was dose-depen-
dent, but the isodose curves stimulated by insulin were dif-
ferent. The maximum reaction dose of normal rats was
1.0  nmol/L, while that of burn-injured rats was
3.0 nmol/L. The isodose reaction curve of burn-­injured rats
constructed based on the maximum reaction percentage
shifted significantly to the right, the ED50 increased, and
the result showed that the sensitivity of cAMP-PDE in adi-
pose tissue of burn-injured rats stimulated by insulin
decreased, and that the maximum reaction was normal.
15  Metabolism in Burns

381
However, both the sensitivity and reactivity of glucose
transfer stimulated by insulin on peripheral tissues (soleus)
obviously decreased. When using a kind of “insulin chemi-
cal mediator” with a molecular weight of 3.0–3.5  kDa,
which was induced in the plasmalemma of normal rat liver
cells by the stimulation of insulin (2 nmol/L), we found
that the chemical mediator could simultaneously stimulate
the activity of cAMP-­PDE in the lipocytes of burn-injured
rats, and was shown to be dose-dependent. However, this
chemical mediator could increase by six times the activity
of cAMP-PDE in normal rats, but only 1.24 times in burn-
injured rats. The result indicated that the reactivity of
cAMP-PDE in adipose tissue to the chemical mediator
stimulated by insulin was obviously suppressed, although
the chemical mediator could multiply the biological effect
of insulin on normal rats about 150 times, and the burn-
injured group showed an “incident” defect post-insulin
receptor. The above-mentioned varied post-burn reactivity
of the insulin receptor signal system may be relevant to the
alteration of insulin receptor intrinsic tyrosine protein
kinase (TPK) activity. This signal transfer disorder may be
an important step in insulin resistance.
4. The activity of the exogenous substrate (histone H2B and
Poly(Glu Tyr)) stimulated by TPK on hepatocytes and skele-
tal muscle plasmalemma of scalded rats with third-­degree
burns covering 30 % of the TBSA increased without the stim-
ulation of insulin, but the activity of exogenous substrate
phosphorylation catalyzed by TPK, which was stimulated by
insulin, clearly decreased. Partly purifying the insulin recep-
tor of hepatocyte and skeletal muscle plasmalemma, we
found that the insulin receptor β-subunit self-phosphorylation
of scalded rats decreased under non-stress condition. Post-
burn receptor phosphorylation stimulated by insulin and the
phosphorylation of receptor TPK catalyzing exogenous sub-
strate clearly decreased. The result suggested that post-burn
insulin receptor might lead to serine/threonine phosphoryla-
tion. This was due to traumatic stress reaction and the activa-
tion of other protein kinase systems (protein kinase
A  and  protein kinase C), thus influencing receptor self-­
phosphorylation. The activity of TPK was suppressed, which
caused the insulin receptor signal coupling disorder.
5. Post-burn hyperglucose and hyperinsulin reaction on one
side may be related to strengthening glycogenolysis and
glyconeogenesis; on the other, more important side is the
fact that glucose uptake suppression of peripheral tissue
(especially muscle) is stimulated by insulin and causes
hyperglucose. This may be closely related to insulin recep-
tor signal coupling suppression, or it may be related to
transmembrane signaling the abnormal transmission of glu-
cose uptake. For this reason we carried out the 14C-­U-D glu-
cose saturation test to assess the dynamic alteration of
glucose transporter binding sites on skeletal muscle plasma-
lemma and intra-cellular membrane (microsome mem-
brane) of burn-injured rats. The result demonstrated that
after severe burn, the binding site of glucose transporter
(mainly GluT4) on muscle cells did not significantly alter,
but the effect of intra-cellular membrane glucose transporter
transferring to plasmalemma stimulated by insulin was
clearly lower than in the normal control group. It indicated
that the decrease in transportation from the intra-cellular to
the cytoplasm membrane of the glucose transporter was the
direct reason for the muscle glucose uptake disorder. This
may be related to the receptor sign coupling disorder due to
the decrease in the ­insulin receptor TPK activity after a
burn. It was also the central link of post-burn insulin resis-
tance and glycometabolism disorder.
15.2.2.2 Clarify Post-burn Insulin Resistance
1. Pre-receptor mechanism: the increase in the post-burn pro-
duction of TNF-α has an important effect on insulin resis-
tance. As a mediator of insulin resistance, TNF-α induces
insulin resistance by way of mediating serine phosphoryla-
tion to suppress tyrosine phosphorylation of insulin recep-
tor substrate (IRS)-1; the functions of leptin and TNF-α
coincide, which is related to insulin resistance mediated by
TNF-α. The amounts of stress hormone produced after
severe burns can antagonize the function of insulin directly.
Resistin is a type of active peptide hormone that is synthe-
sized and secreted by adipocytes, which can weaken the
effect of insulin, reduce glucose tolerance, and participate
in the regulation of insulin resistance.
2. Receptor mechanism: a severe post-burn hyperinsulin reac-
tion induces insulin receptor endocytosis on hepatocytes and
reduces the receptor on the membrane; thus, the sensitivity to
insulin decreases. After combining with its receptor α-subunit,
insulin promotes self-phosphorylation of tyrosine residue in
the β-subunit cytoplasmic region to activate TPK. Because
the self-phosphorylation function of β-subunits in liver and
muscle decreases after a severe burn, the TPK activity of the
receptor is affected. Because of the burn wound becoming
infected and gut-originating translocation, endotoxemia often
occurs, which clearly reduces the reactivity to insulin of insu-
lin receptor TPK activity in rat sarcolemma.
3. Post-receptor mechanism: the serine/threonine phosphor-
ylation of IRS-1 is one of the important negative feedback
mechanisms in insulin signal transduction. It inhibits tyro-
sine phosphorylation of IRS-1; thus, it influences the inter-
action of IRS-1 with insulin receptor and the signal of
insulin transmission downstream. The serine on different
sites of IRS-1 has different actions. Ser307 has significant
action on the negative feedback mechanism of insulin sig-
nal transduction; its hyperphosphorylation would induce
insulin resistance. The Institute of Burn Research of the
Second Military Medical University verifies a post-­burn
IRS-1 307Ser phosphorylation increase; thus, tyrosine
phosphorylation clearly decreases, which is one of the
important molecule mechanisms of post-burn insulin
resistance.
15.2  Glycometabolism

382
4. Post-burn islet β-cell insufficiency is the important link
between MODS and glycometabolism disorder:
(a) The post-burn △INS30/△GLU30 (the ratio of serum insulin
increment to blood sugar increment after 30 min of sugar
loading) decreases. The △INS30/△GLU30 is not affected
by the level of fasting blood glucose and fasting serum insulin;
thus, it can be used as the quantitative assessment index for the
insulin early rapid secretion function. If the △INS30/△GLU30
of severe burns and of patients with other injuries clearly
decreases, it indicates that the early secretion function of islet
β-cells in these injured patients also decreases.
(b) Homeostasis model assessment of β-cell function
(HOMA-β) can be used as a quantitative assessment index
for islet β-cells to assess the level of continuous insulin
secretion under the stimulation of fasting blood glucose
(basic condition). The glucose level remains stable, the
insulin is secreted steadily and continuously, when in a
steady state without strenuous exercise after fasting for
8 h. The formula HOMA-β = fasting insulin × 20/(fasting
blood glucose-3.5) is not applicable for the glucose evalu-
ation of hypoglycemic burns patient when fasting blood
glucose is below or equal to 3.5 mmol/L. HOMA-β of
severe burns, including patients with other injuries, clearly
decreases, indicating that the level of the basal insulin
secretion function of burns patients decreases too.
15.2.2.3 Identify the Function of Some
Adipocytokines in Post-burn
Glycometabolism Disorder
Recently, some research has certified that adipose tissue
has the endocrine function, i.e., it can produce and excrete
different kinds of adipocytokines, including TNF. Because
of the stress, infection, and inflammation reaction after
severe burns, adipocytes and inflammatory cells may
release amounts of the abovementioned adipocytokines to
induce insulin resistance, decrease the sensitivity and reac-
tivity of the tissue to insulin, thus causing post-burn glyco-
metabolism disorder with other excitable hormones to
elevate the blood sugar, even having a more significant
effect than the latter.
The post-burn inflammation reaction is a defensive reac-
tion of the organism with regard to external irritation, the
reaction is sometimes expressed excessively. Severe bacte-
rial infection of the wound or endogenous post-burn infec-
tion are the important causes of excessive inflammation. It
is known that various inflammatory cytokines and APRP
(acute phase reactive protein) take part in insulin resistance,
mainly TNFα, IL-6, and C-reaction protein. Those inflam-
matory cell factors may be important in inducing post-burn
insulin resistance. A series from our research shows that
under the conditions of severe burns TNFα is clearly posi-
tively correlated with the degree of insulin resistance.
TNFα can induce insulin resistance in normal Kunming
mice that is dose-­dependent and time-dependent. TNFα
causes insulin resistance by promoting the increase in the
insulin antagonistic hormone, and suppressing glucose
uptake stimulated by insulin and the activity of tyrosine
protein kinase in insulin receptor β-subunit on the histio-
cyte membrane.
The fact that post-burn FFA and inflammatory cell fac-
tors cause islet β-islet cell injuries and function defects is
the important link in glycometabolism disorder. TNFα
induces islet β-cell injuries through the function of NO,
which is related to NF-κB gene expression. NO and TNFα
in endotoxemic burn rats can suppress the function of islet
β-cell for insulin synthesis and excretion function stimu-
lated by various glucose concentrations. The TNFα level
in the blood of severe burns patient is clearly negatively
correlated with HOMA-β. An experiment in vitro shows
that IL-1 can cause islet β-cell apoptosis and necrosis.
These results imply that inflammatory cell factors of
severe burns patient take part in the injuries of islet β-cell
function. The research of the 94th Hospital of the PLA
suggests that the injuries or insufficiency of islet β-cell
function should be the important components of post-burn
MODS, which has been of great significance in the clinic.
15.2.3
Glycometabolism Disorder
15.2.3.1 The Therapeutic Schedule of Post-burn
Glycometabolism Disorder [43–55]
Excessive Inflammatory Reaction Decreased by
Anti-infection
1. Strengthen control of burn infection: glucose control is
related to infection control post-burn. The Burn Institute
of The Third Military Medical University proposed that
early enteral nutrition could strengthen the protection
of the intestinal barrier and reduce the intestinal trans-
location after a burn injury, which is one of the most
important measures in preventing and curing post-burn
glycometabolism disorder. Debridement and prompt
closure of the wound, making rational use of antibiot-
ics, and strict disinfection are of importance for the pro-
phylaxis and treatment of post-burn glycometabolism
disorder.
2. The anti-inflammatory of insulin and soluble inflamma-
tory factor receptor: the research of the 94th Hospital of
the PLA showed that insulin and sCD14 had an antago-
nistic effect on inflammatory cytokines. Insulin can
reduce the level of burn-injured inflammatory cyto-
kines, it has an antagonistic effect; therefore, it can play
an important role in the prevention and cure of burn-
injured MODS. Animal study has proved that sCD14
can reduce the inflammatory cytokine level of severely
burn-injured rats.
15  Metabolism in Burns

383
3. Reduce the stress response of burn patients: the 94th
Hospital of the PLA, etc., proposes the moderation idea
of glucose stress post-burn. It suggests that a lack of glu-
cose stress and an excess of glucose stress could both
lead to an unfavorable prognosis. Sedative, analgesic,
and Chinese traditional treatment such as acupuncture
can reduce the level of burn stress hormone and glucose.
The New Use of GIK in Burn Therapy
Using GIK to treat burns patient individually, which is pro-
posed by the 94th Hospital of the PLA, is another exemplifi-
cation of “old drug, new use”; after aspirin, individualized
GIK therapy supplies carbohydrate, lowers blood glucose, is
anti-inflammatory, protects the islet β-cells, modulates bowel
function, and improves nutrition.
1. Further recognition of GIK therapy: the 94th Hospital of
the PLA suggests that the prohibition or decrease in glu-
cose infusion when burn hyperglycemia occurs might
be a passive therapy. Post-burn hyperglycemia is the
expression of the glycometabolism disorder. It does not
mean that the organism need not supply glucose; using
insulin separately to control glucose cannot achieve the
goal of nutritional supplementation. The research of the
94th Hospital of the PLA suggested that the combina-
tion of insulin and glucose might improve nutrition,
antagonize inflammation, and protect islet β-cells; it is
necessary and useful in preventing post-burn MODS.
2. Individualized GIK therapy
(a) The theoretical reference formula of the individualized
GIK therapy. The 94th Hospital of PLA calculates the
theoretical guidance for the amount of insulin accord-
ing to the following formula based on fasting blood glu-
cose concentration (mmol/L), body weight (kg), and
the amount of glucose infusion (g). GIK insulincon-
sumption 
consumption 
= 
(fasting 
blood 
glu-
cose × 18 − 100) × weight ×  0.003 +  infused  glucose/n.
The more severe the glucose resistance, the lower the
level of insulin secretion, the smaller the n value.
Normally n = 4, i.e., glucose/insulin is one fourth in the
routine GIK prescription. KCl is added according to the
ratio of KCl/glucose in routine GIK prescription. The
theoretical guidance for the amount of GIK insulin is
formulated by referencing the content in “Medical Care
Operative Technique in Army Troops” (the fourth edi-
tion)
on
Page
621.
[(fasting 
blood 
glu-
cose × 18 − 100) × weight × 0.003] is the insulin dose to
control the above-normal fasting blood glucose
(5.6  mmol/L) to normal levels. Infused insulin
(glucose/n) promotes the effective utilization of infused
glucose. The 94th Hospital of the PLA analyzed with
linear regression (using SPSS11.0 for Windows) the
data of individualized GIK prescription according to
the ideal effects that we could achieve. We propose the
empirical formula to express the relation among insulin
consumption (y), fasting blood glucose (x1), and body
weight (x2) of injured patients: the guidance insulin
needs
(U)
for
10 
%
glucose
500 
ml/L,
y = 3.309x1 + 0.251x2–22.758.
(b) Matters needing attention for individualized GIK
therapy. We calculate the reference insulin dosage in
GIK according to the theoretical and empirical for-
mula. In the course of GIK infusion:
(i) Close observation of serum glucose, potassium,
BP, pulse, and consciousness, avoid hypoglyce-
mia shock and hyperkalemia.
(ii) The duration of infusion of GIK (500 ml) and
instilling KCl (1  g) should not be less than
40 min.
(iii) The dosage of insulin should start with a small
dose, then increase gradually.
(iv) The ideal effects of GIK therapy is that the
fasting blood glucose level is maintained at
5.0–6.1  mmol/L.  Eliminate the IR-inducing
factors, such as necrotic tissue and infection,
supply an appropriate amount of Mg, Ca, vita-
min C, ATP, etc.
15.3
Protein Metabolism
Yinling Tan, Linshui Xu and Yanling Dong
15.3.1
Explore the Mechanism of Protein
Metabolism Changes After Burn
Injury [56–61]
A series of experimental animal models and methods were
established for the determination of the changes in protein
metabolism.
Full thickness burns covering 37 % of the TBSA were
administered on the back and one hind leg of rats by hot
water scalding under general anesthesia. Urinary 3-methyl-­
histidine was determined to define whether the rats enter into
the hypermetabolic period 3 days after scalding injury. Full-­
thickness burn was confirmed by skin biopsy. The relation-
ship between the change in protein degradation and the
synthesis rate in the scalded and remote regions of the skel-
etal muscle was investigated.
Fluorescence spectrophotometry was used to measure the
incorporation and release rate of 3H-tyrosine from soleus
muscle. Seventy-two hours after injury, the soleus muscle of
the scalded leg, its unscalded counterpart, and the legs of the
normal control animals was isolated and its protein metabo-
lism was investigated in  vitro. It was found that tyrosine
incorporation, tyrosine release, and tyrosine net release of the
15.3  Protein Metabolism

384
soleus from the scalded limb were 33, 24, and 17 % higher
than those from the unscalded leg (p < 0.01) respectively.
There was no significant difference in parameters between
the unscalded leg of the scald rat and the normal control. It is
strongly suggested that the increased decomposition of the
muscular protein at the site of the burn injury might be the
main cause of a negative nitrogen balance after burns.
The protein degradation rate, the activities of cathepsin B,
H, L, and D, and the neutral protease were studied in the soleus
muscle of the scalded and healthy legs. The effects of a large
dose of intraperitoneal insulin or Na-DL-e-­hydroxybutyrate
on these proteases were also observed. It was found that on the
3rd day after injury, the protein degradation rate and the activi-
ties of cathepsin B, H, L, D, and neutral protease increased
significantly in the soleus muscle of the scalded limb, but no
similar changes could be seen in that of the unscalded limb
and the normal control. Activities of cathepsin B, H, L, and D
were significantly inhibited by an intraperitoneal injection of
insulin. These findings suggest that cathepsin might play an
important role in the protein degradation of the injured skeletal
muscle in the early stages of severe burns and might be one of
the causes of negative nitrogen balance. Insulin can be protein-
sparing because of its inhibition on cathepsin, although there
may be insulin resistance in scalded rats.
One hind leg of the rat (about 7 % of the TBSA) was scalded
and the changes in the reduction oxidation state and protein
degradation in the soleus muscle were observed 72  h after
scalding both in vitro and in vivo. It was found that the ratios
of lactate/pyruvate (L/P) and malate/pyruvate (M/P) of the
soleus muscle were significantly lower and the protein degra-
dation rate significantly higher in the scalded legs than in the
unscalded legs and the normal control. After the addition of
insulin to the medium, a significant elevation in the ratios of
L/P and M/P and a reduction in the protein degradation rate
were observed in the soleus muscle of scalded legs. These find-
ings suggest that there might be a good correlation between the
changes in the reduction oxidation state and the protein degra-
dation rate in the cytosol of the soleus muscle of scalded rats.
The changes in the selenium metabolism, glutathione per-
oxidase activity, and lipid peroxide content in the tissues of
rats suffering from full thickness scalding of 30 % of the
TBSA were observed in the first 7 days after injury. It was
found that selenium content in the rat tissues decreased
markedly after injury, which in turn resulted in a serious
reduction in the glutathione peroxidase activity and a signifi-
cant increase in lipid peroxides in the serum, erythrocytes,
and liver; however, the muscular tissue showed no significant
changes. These facts imply that after burn injury, the body
might be in a state of selenium deficiency, the loss of sele-
nium might be responsible for the reduction in the anti-­
peroxidation ability of glutathione peroxidase, and
consequently, an increase in the lipid peroxides in tissues.
Only the muscular tissue is insensitive to lipid peroxidation.
It is believed that the reduction in the anti-peroxidation abil-
ity of glutathione peroxidase after burn injury might be one
of the main causes of intensification of the injury resulting
from free radicals.
An in vitro transcription system was used to determine the
activity of transcription in skeletal muscle after burn injury. It
was found that the protein and DNA levels of the liver showed
no obvious changes after scalding, but the RNA content
increased by 24 % and the rate of leucine incorporation by
31  %. After the addition of insulin, the leucine content
increased by 23 and 25.8 % in the controls and the injured
animals respectively. The results indicate that the rate of pro-
tein synthesis in the liver of the scalded animal increases,
which is likely to be related to the increase in RNA content,
and the liver protein synthesis remains sensitive to insulin.
Two-dimensional electrophoresis (2-DE) was employed to
identify the downregulating proteins among the differential
proteins in scalded rats. Spot detection and matching were
performed using Image Master 2D Elite. Mass spectrometry
was performed on Bruker Biflex III time of flight (TOF).
There are 34 proteins in the intestinal mucosa of scalded rats,
which were downregulated at PBH 6 and 12. Among them 22
proteins were employed for identification and analysis. Six
proteins, mitochondrial aconitase, alpha-propionyl-CoA car-
boxylase, heavy chain A of F1-ATPase in rat liver, troponin-1,
short-chain of hydroxylacyl-­coenzyme A dehydrogenase, and
alpha-­subunit of P-electronic transferring flavoprotein (ETF),
were downregulating proteins correlated with mitochondria in
the intestinal mucosa of severely scalded rats. Triosephosphate
isomerase 1 and cytosolic epoxide hydrolase were downregu-
lating proteins participating in the metabolism of scalded rats.
Fibromodulin, dynein-like protein, troponin-2, and myosin
light chain 3 alkali (MLC) were downregulating proteins cor-
related with cellular skeletal protein. Glucocorticoid-­inducible
protein, nuclear factor1-B2, BRCA1, transcriptive factor EB
(estradiol benzoate), β2 subunit of G-protein, and N-methyl-
D-aspartate receptor1 (NMDAR) were downregulating pro-
teins participating in the post-burn regulation of intestinal
mucosa in scalded rats. T-cell receptor-V-delta 6 and Ig heavy
chain V region protein 1 were downregulating proteins that
correlated with the immunomodulation of intestinal mucosa
in scalded rats. The conclusion was drawn that the downregu-
lating proteins of the intestinal mucosa in scalded rats were
closely related to mitochondria.
15.3.2
Explore the Regulatory Mechanism
of Enhanced Protein Catabolism
in Post-burn Rats
A BALB/c mice model was established with full-thickness
scalding of 18–20 % of the TBSA, including the back and
one hind limb. The catabolic rate of protein of the soleus
15  Metabolism in Burns

385
muscle was reflected with the net tyrosine-releasing rate.
The protein catabolic rate and tumor necrosis factor (TNF)
content of the soleus muscle of the scalded region and remote
region were dynamically determined in the first week after
the rats had been subjected to full thickness scalding. It was
found that first, the progressive aggravation of protein catab-
olism of the skeletal muscles of both the scalded and remote
regions, especially the scalded region, was the main cause of
negative nitrogen balance after thermal injury. Second, the
TNF content of skeletal muscles was much higher in the
scalded region than in the remote region, but the TNF
increases of the two regions were significantly correlated and
increased gradually in a similar content–time curve. TNF
increase was also significantly correlated with the protein
catabolic rate of the skeletal muscles. These facts imply that
the TNF increase of the muscles of the remote region might
be affected by that of the scalded region, and that the local
high TNF content might be an important cause resulting in
increased protein catabolism. Third, exogenous TNF mono-
clonal antibodies could block the effects of endogenous
TNF, which suggests that cytokine antagonists might be new
therapeutic agents for certain diseases. Fourthly, TNF pro-
duction after severe scalding was stimulated by local inflam-
mation and subsequent wound infection and the latter played
an even more important role [62–67].
After injury, the level of IL-1 of the plasma, injured and
uninjured limbs were all increased, and reached the summit
at PBH 48, but those of the injured limbs were much higher
than those of the uninjured ones; the levels were then gradu-
ally decreased by 72 h. The protein catabolic rate of unin-
jured limbs was higher than normal at 48 h, but it regained a
normal level at 72 h. The rate of injured limbs was signifi-
cantly higher than that of normal and uninjured limbs 72 h
after scalding. The hrIL-1 enhanced the protein catabolic
rate and the activities of lysosomal proteolytic enzymes in
the soleus muscle of normal mice in vivo and in vitro respec-
tively. Overall, in the early stages of scald injury, IL-1 could
enhance the lysosomal protease activity, increase the protein
catabolic rate in skeletal muscle, and promote the negative
nitrogen balance directly. These effects may not depend on
the actions of emergent hormones.
The protein catabolic rate (TNR) and the level of IL-6 in
the soleus muscle and serum were determined and the effects
of IL-6 on TNR of normal mice and those of IL-6 antiserum
on TNR of the scalded mice were observed during the first
week after scalding. The level of IL-6 was significantly
increased and this was maintained during the first 3 days.
TNR of the scalded leg was increased to the peak on the 3rd
day and then decreased gradually, while that of the unscalded
leg was increased only on the 2nd day after scalding. TNR
was significantly increased when IL-6 was injected into the
normal mice and IL-6 antiserum could significantly inhibit
the increased TNR of the scalded mice when injected intra-
peritoneally. The increase in IL-6 is related to local inflam-
matory response in the early stage after scalding and the high
level of IL-6 can increase the catabolic rate of muscle
protein.
The effects of endotoxin on the catabolic rate were also
examined. It was found that the protein catabolic rate was
markedly accelerated in the scalded soleus 3  days after
injury, and showed no significant changes in the healthy one,
in which the protein catabolic rate was near or similar to that
of the normal control. After 2 mg/kg of endotoxin had been
administered intraperitoneally, the findings were as follows:
(a) Endotoxin could also accelerate the protein catabolic
rate in the skeletal muscles.
(b) The protein catabolic rate in the scalded soleus did not
increase further and no summation effect of scalding and
endotoxin on protein catabolism occurred
Based on the above, it can be seen that cytokines play an
important role in the protein catabolism in scalded regions
post-burn. As cytokines have the activities of chemotaxis of
inflammatory cells and paracrine functions, TNFα, IL-1, and
IL-6 in the injured limbs can play roles in the chemotaxis of
inflammatory cells locally, such as ­leucocytes and macro-
phages, and further activate them to generate new TNFα,
IL-1, and IL-6 that produce a more marked effect on protein
catabolism.
15.3.3
Explore the Protein Degradation
Pathway and Regulatory Factors
in Burn Rats
The main proteolytic pathway induced by severe burn injury
was determined. The level of ubiquitin was further exam-
ined by Western blot analysis. When the ATP–ubiquitin–
proteasome
complex-dependent
proteolytic
system,
lysosomal cathepsin system, and Ca2+ dependent proteolytic
system were maximally inhibited after the burn, the
increased blockade in the proteolysis of the injured limb
was 85.7, 35.25, and 4.7 % respectively. Additionally, the
content of ubiquitin had a markedly progressive enhance-
ment on the 1st, 2nd, and 3rd day after scalding. Such a
severe burn causes intense activation of an ATP–ubiquitin–
proteasome complex-­dependent proteolytic process, which
accompanies the notable increase in ubiquitin content.
[68–72].
In order to study the role of 20S protease in the formation
of negative nitrogen balance after burn injury, rabbits were
immunized with the purified enzyme, and the antiserum with
a value 1:32 was obtained. The rats afflicted by third-degree
scalding injury covering 37 % of the TBSA were used as the
animal model and the changes in the content and the activity
of the 20S protease in scalded rats’ muscle were observed by
means of immunoprecipitation and Western blot analysis
15.3  Protein Metabolism

386
with application of the antiserum. Within 3 days after burn-
ing, the 20S protease activity in both the injured and unin-
jured limbs increased markedly. On the 2nd and 3rd days
after the burn, the 20S protease content of the injured and
uninjured limbs also increased markedly too. The increase in
the content and activity of 20S protease in the severely
burned rats was significantly correlated with the formation of
negative nitrogen balance after the burn. This provides a new
pathway to avoid the formation of the negative nitrogen bal-
ance after the burn.
The content of ubiquitin (Ub) and the amount of tyrosine
released in the scalded and remote regions were determined
to study the mechanism of intensified proteolysis of skeletal
muscles after severe scalding in rats and its relationship
with TNFα. Twenty-four hours after TNFα injection, the
expression of Ub protein and mRNA and the amount of
tyrosine in the soleus were significantly increased. The Ub
content and the amount of tyrosine release were signifi-
cantly increased with a similar tendency in the scalded limb;
in the un-scalded limb, the increase in Ub content was
observed, but no significant increase in tyrosine was found.
After the treatment with TNFα, Ub content and the amount
of tyrosine release in the soleus were markedly increased in
both the scalded and the unscalded limbs, but the changes
were more marked in the scalded limbs. The combined
effects of scalding and TNFα were clearly observed. The
results suggested that the production of a certain amount of
TNFα induced by scalding itself might act on the
Ub-dependent system to promote proteolysis of the skeletal
muscles in the scalded region.
The means of immunoprecipitation deduction and ELISA
were used to test the activities and contents of 26S protea-
some and 19S regulator in the skeletal muscle of rats afflicted
with third-degree burns covering 30 % of the TBSA. The
results showed that the activities and contents of 26S protea-
some and 19S regulator in skeletal muscle were markedly
raised by TNFα after scalding. The results indicated that
TNFα activates the 26S proteasome system in skeletal mus-
cle; thus, it enhances the degradation of protein, which is
associated with the development of negative nitrogen bal-
ance following scalding.
To compare the effect of different routes of nutritional
support on the 26S proteasome, the change in activities, the
contents of the 26S proteasome, and the rate of protein
­degradation in the skeletal muscle of scalded rats with the
animal model of enteral feeding and parenteral nutrition
were tested. Compared with parenteral nutrition, enteral
feeding could markedly reduce the activity and content of
the 26S proteasome, and the release of tyrosine was also
lowered. The results suggested that early enteral feeding
might distinctly inhibit the system of 26S proteasome, and
reduce the protein degradation in skeletal muscle in burned
rats.
15.3.4
Explore Methods of Improving
and Correcting Negative Nitrogen
Balance
There are at least three pathways to prophylaxis and regulat-
ing the post-burn metabolism for the reduction or inhibition
of protein catabolism: nutritional support, hormone, and
medicines [61, 72–81].
15.3.4.1 Nutritional Support
Nutritional support is necessary for burns treatment to pro-
vide an adequate intake of calories and protein to improve
the body’s metabolism. There are three aspects of the nutri-
tional support that need to be considered:
1. Route of administration: parenteral nutrition (TPN) plays
an important role in the treatment of heavy patients, but
the long-term use of TPN may lead to mucosal atrophy,
which may promote enterogenous infection and enterog-
enous hypermetabolism. EF is in line with physiological
characteristics and may stimulate mucosal proliferation
and repair. The intestines are the body’s largest immune
organ, and contain 40 % of the total number of immune
effector cells in vivo, which accounts for secretion of a
variety of cytokines. Enteral feeding can maintain the
production of mucosal immunoglobulin A and inhibit the
release of proinflammatory mediators.
The researchers at the Burn Institute of Southwest
Hospital have studied nutritional support for many years.
They consider that early enteral feeding after burn injury
can be effective in maintaining intestinal structure and func-
tion, reducing endotoxin translocation, adjusting the activa-
tion of liver Kupffer cells, and decreasing the content of
hormones, TNF, and IL-8. In addition, early enteral feeding
can obviously ameliorate MODS in rats with severe burns.
On these grounds, early enteral feeding could improve
the ischemia and hypoxia of the gastrointestinal tract, reduce
the absorption of gut-derived endotoxins and the associated
release of inflammatory mediators, block the interaction
circle of intestinal infections and inflammatory mediators,
lessen the inflammatory response to a variety of internal
organs and be involved in the amelioration of visceral func-
tional lesions after burn injury. Early enteral feeding also
significantly reduced the release of tyrosine in rat soleus
muscle and 20S multifunctional protease activity.
The ATP–ubiquitin-dependent 26S proteasome system
is the major means of muscle protein degradation and
plays an important role in post-burn hypermetabolism
mechanism. TNF and IL-1 and other cytokines produced
after burn injury can activate the 26S proteasome system
and enhance the protein degradation, which are the impor-
tant reasons for body weight loss, hypoimmunity, and
organ damage. Early enteral feeding can reduce the levels
of TNF and other inflammatory mediators, is thus condu-
15  Metabolism in Burns

387
cive to regulating the activation of 26S proteasome sys-
tem, and results in an overall reduction in skeletal muscle
protein catabolism.
2. Time of administration: most studies suggest that if the gut
works, enteral feeding can be administered as early as pos-
sible after burn injury; it is superior to delayed feeding
post-burn. The urinary output of nitrogen and 3-MH during
the first 24 h was significantly lower in burn patients with
early enteral feeding than those with delayed feeding.
3. Composition of nutrient solution: the nutritional compo-
sition post-burn proposed by many researchers, composed
of glutamine, branched-chain amino acids (BCAA), argi-
nine, ω-3 fatty acids, RNA, growth hormone, etc. Among
them, arginine and glutamine are called immunoenhance-
ment nutrients because of their roles in the promotion of
immunological function. BCAA in the human liver ca not
effectively metabolize; thus, its oxidation proceeded
mainly in muscle. BCAA can be used in stress patients
with burns to reduce muscle protein breakdown and pro-
mote protein synthesis. The BCAA dosage of burns
patients is still inconclusive, and it may be appropriate to
give 0.2–0.5  g/(kg · d). β-hydroxybutyrate sodium can
­significantly reduce the output of 3-methyl-­histidine,
which shows its clear effect of nitrogen conservation.
Glutamine is a metabolic substrate that it is essential
for the intestinal mucosa. In the process of repairing the
intestinal mucosa after burn injury there is an increased
demand for glutamine. Adding L-glutamine into the
intestinal nutrient solution can help to maintain the intes-
tinal mucosa barrier and reduce protein catabolism in
skeletal muscle. Glutamine is also a conditional essential
amino acid with a blood concentration of 600, 650 μmol/L,
and it has the highest concentration among amino acids in
plasma; however, its concentration in the muscle cells is
about 30 times that in blood; more than half of free amino
acids in skeletal muscle is Gln. After burn injury, the Gln
concentration was significantly decreased, and the resting
energy expenditure (REE), DAO activity, and the levels of
TNF, LPS, and IL-1 were markedly increased. Correlation
study showed that REE bears a negative correlation with
Gln concentration. It is obvious that Gln supplementation
could abate the degree of intestinal injury, lessen intesti-
nal mucosa permeability, reduce the plasma inflammatory
mediators and attenuate enterogenous hypermetabolism.
In addition, Gln supplementation could promote protein
synthesis, abate protein decomposition, speed up the
wound healing rate, and significantly reduce the hospital
stay. Studies showed that Ala-Gln-supplemented TPN in
burn rats and/or patients can promote protein anabolism,
improve nitrogen balance, and attenuate the intestinal
mucosa atrophy and Gln decline in muscle.
Arginine, a nonessential amino acid, becomes essen-
tial when the body is subjected to metabolic stress situa-
tions such as trauma, burns, surgical operations, cancers,
and sepsis. This important immuno-nutrient is required
supplementation under these pathological conditions. The
proliferation and differentiation of lymphocytes and the
production of cytokines is supported by arginine. It also
participates in maintaining the activities of monocytes,
neutrophils, and lymphokine-activated killer cells (LAK).
Sodium β-hydroxybutyrate can also significantly reduce
3-methyl-histidine output, which showed a clear effect on
nitrogen conservation, but failed to prove that sodium
β-hydroxybutyrate could inhibit the activity of cathepsin.
In addition, ornithine α-ketoglutarate (OKG) is a dra-
matic preparation, which is not only a precursor of glu-
tamine and arginine, but also precursors of other amino
acids and α-keto acid. They play an important role in the
control of protein metabolism, and can antagonize pro-
teolysis, reduce the release of amino acids from muscle,
abate the level of glucogenic amino acid such as threo-
nine and serine and so on, improve the nitrogen balance,
increase the content of pre-albumin and retinol binding
protein, and reduce the level of hyperphenylalanin-
emia.  The preparation containing both medium-chain
­triglyceride (MCT) and long-chain triglyceride (LCT),
MCT/LCT, for enteral nutrition can more effectively
reduce protein breakdown compared with the prepara-
tion only containing LCT after burn injury, and MCT/
LCT could elevate the level of serum albumin leading to
an improved nutrition status of burn patients.
15.3.4.2 Hormones
The use of recombinant human growth hormone (rhGH) in the
treatment of patients with severe burns was studied. The prompt
post-burn administration of rhGH could regulate post-burn
hypermetabolism in severely burned patients by increasing the
plasma levels of growth hormone (GH), IGF-­1, and insulin,
which was beneficial to the improvement of the nutritional
state and to the promotion of protein synthesis and wound heal-
ing. The optimal time to give rhGH to severely burned patients
may be during PBD 7–9. The synergistic effect of rhGH and
IGF-1 on promoting wound healing and increasing protein
anabolism has been found in rats with burn injury.
15.3.4.3 Drugs
Cytokine antibodies, glucocorticoid receptor antagonists,
and proteasome inhibitors can also inhibit muscle protein
catabolism. There is strong evidence that the regulation of
metabolism can be adjusted at the genetic level after a burn;
thus, gene therapy is one possibility, for instance, calcium
antagonist dantrolene can downregulate the gene expression
and activity of the ubiquitin–proteasome system.
Another possibility in the future may be the induction of
heat shock response. Studies have shown that high levels of
heat shock protein expressed in cells and tissues may be
15.3  Protein Metabolism

388
opposed to the destructive stimulus. For example, the induc-
tion of heat shock response may be in opposition to the effect
of dexamethasone on muscle protein degradation, suggesting
that glucocorticoid-mediated protein degradation in muscle
can be blocked by the heat shock response. In addition, endo-
toxin and cytokines produced from local regions afflicted
with a burn is one of the sources of cytokines in the blood;
thus, escharectomy during the early stages post-burn may
also help to reduce protein catabolism in skeletal muscle.
15.4
Growth Hormone and Metabolism
Shilin Deng
15.4.1
Regulatory Effect of Growth Hormone
on Glucose and Protein Metabolism
in Burn Patients [82–84]
The Burns Institute of Tianjin, from 2000 to 2002, observed
24 cases of severely hospitalized burns patients aged 28.7 ± 7.6
with TBSA/third-degree burn covering 70.40 % ± 17.71 %/
24.40 % ± 23.51 % of the TBSA. On the basis of conventional
burn treatment, the daily application of rhGH by 0.2–0.25 U/
kg·day was started from the 4th to the 14th day after the burn.
15.4.2
Growth Hormone Regulation
of the Glucose and Protein
Metabolism for Burns Patients
1. Changes in blood glucose after a burn: the normal range
of blood glucose is 3.84–6.05 mmol/L. If it is higher than
3.84–6.05 
mmol/L
hyperglycemia
is
diagnosed
(Table 15.23).
2. Comparison of coma serum total protein levels in two
groups of patients: changes in serum total protein before
and after rhGH treatment. From Table 15.24, we can see
that serum total protein and albumin levels are signifi-
cantly increased, and it suggests to us that the application
of rhGH can promote the role of protein synthesis in
the body.
3. Comparison of serum albumin level in two groups of
patients (Table 15.25)
4. The relationship between the time of starting to use rhGH
and the incidence of f hyperglycemia (Table 15.26)
5. Regulation of rhGH on the glucose metabolism after
a burn
(a) Blood glucose of severely burned patients increases
in the 2 weeks after a burn. After 0–3 days, 4–7 days,
and 8–14 days the increased rate of glucose is 52.38,
50.24, and 20.00  % respectively. However, if the
application of rhGH starts 1 week, 2 weeks and after
2 weeks after the burn, the increased rate of blood
glucose is 100, 50, and 0 %.
(b) Severely burned patients are affected by a severe stress
reaction in the early days. At the same time, as a result
of changing the number and function of insulin recep-
tors on the cell membrane, GH can inhibit glucose
elimination through the non-oxidation pathway and
transfer by cells; thus, the early application of rhGH
leads to a serious obstacle to glucose metabolism.
(c) The application of rhGH is in direct proportion to the
severity of burns, using time and dose. Because of the
conclusion above, the proposed application of rhGH
Table 15.24  Comparison of serum total protein levels between the
two groups of patients g L
/
, x
s
±
(
)
Groups
Case number (n)
Pre-medication
Medicated 2 weeks
GH
16
52.67 ± 7.68
62.62 ± 5.87*,#
Control
14
55.65 ± 7.19
57.36 ± 6.88
Note: compared with pre-medication, *p < 0.01; compared with the
control group, #p < 0.05
GH growth hormone
Table 15.25  Comparison of two groups of patients with serum albu-
min levels g L
/
, x
s
±
(
)
Groups
Case number (n) Pre-medication Medicated 2 weeks
GH group
16
26.48 ± 4.65
36.68 ± 4.49*
Control group 14
27.18 ± 1.80
28.57 ± 3.46
Note: compared with before treatment *p < 0.05
Table 15.23  Blood glucose changes within 2 weeks after the burns
x
s
±
(
)
PBD (days)
Case number
Blood glucose
(mmol/L)
Incidence of
hyperglycemia (%)
0–3
21
7.06 ± 3.50*
52.38
4–7
26
6.60 ± 2.04**
50.24
8–14
24
5.42 ± 1.05
20.00
Note: Normal (4.94 ± 0.55), compared with normal number, *p < 0.05,
**p < 0.01
PBD post burn day
Table 15.26  The relationship between the time of starting to use
rhGH and the incidence of hyperglycemia
Time starting to use rhGH after
burn (days)
Case number
Incidence of
hyperglycemia (%)
4–7
5
100.00
8–14
6
50.00
>15
13
0.00
15  Metabolism in Burns

389
in severely burned patients should avoid the peak of
the stress response, and use in the 1–2 weeks after-
ward is appropriate.
6. Regulation of rhGH on protein metabolism after a burn
(a) Serum total protein and albumin levels in patients with
large area burns are significantly lower than normal
after 2–3 weeks, but serum total protein and albumin
with use of rhGH for 2 weeks are higher than before
treatment (p < 0.01) and the control group, i.e., GH
plays a role in the promotion of protein synthesis.
(b) The role of rhGH in promoting protein synthesis is
mediated by IGF-1, and the application of rhGH can
significantly raise serum IGF-1 levels; thus GH is
considered to be an effective promoter in the process
of protein synthesis.
15.4.3
Regulatory Effect of GH
on Hypermetabolic Response
After Burns [85]
The Tianjin Institute of Burns, between 2002 and 2004 used
rhGH as conventional treatment in 32 severely burned patients,
aged 18–49 years, with a TBSA/third-degree burn area of 54.
59 % ± 13.38 %/22.34 % ± 16.25 % of the TBSA. The amount
of rhGH in group A was 0.25 U/kg·day, starting from the 7th
day after the burn and continued for 3 weeks, and in group B,
the control group, who received saline, energy consumption
and hormonal changes were observed.
1. The changes in REE and NPRQ after burns (Table 15.27)
2. The changes in plasma hormone levels, inflammatory medi-
ators and cytokines after burns (Tables 15.28 and 15.29).
Table 15.28  Changes in the plasma hormone level in burn patients x
s
±
(
)
Group
Case number
Monitoring indexes
PBD
1
7
14
21
A
16
Insulin (mU/ml)
22.44 ± 7.60
30.32 ± 5.16
48.97 ± 7.08*
42.77 ± 6.67*
B
16
20.51 ± 8.38
25.49 ± 6.58
30.33 ± 8.25
34.41 ± 11.52
A
16
Glucagon (ng/L)
32.54 ± 9.60
14.79 ± 6.08
28.18 ± 4.26*
21.71 ± 4.43*
B
16
32.24 ± 6.45
16.85 ± 7.3
18.22 ± 4.74
15.05 ± 3.99
A
16
GH (μg/L)
2.09 ± 1.17
2.56 ± 1.05
13.48 ± 2.64**
6.60 ± 2.23*
B
16
1.87 ± 0.45
4.09 ± 1.11
3.68 ± 1.17
2.99 ± 0.88
A
16
IGF-1 (μg/L)
133.6 ± 24.37
126.33 ± 20.55
339.50 ± 84.75**
210.57 ± 57.91*
B
16
92.93 ± 11.51
82.37 ± 13.28
64.47 ± 10.46
57.80 ± 7.60
Note: compared with group B, *p < 0.05, **p < 0.01
Table 15.27  The changes in REE and NPRQ after burns x
s
±
(
)
Groups
Case number
Monitoring indexes
PBD
1
7
14
21
A
16
REE (kJ/day)
8,505.76 ± 2730.92
10,502.46 ± 2095.64
12,688.14 ± 1389.98*
9,011.37 ± 1667.78
B
16
8,694.02 ± 2142.41
10,702.68 ± 1692.23
9,436.14 ± 1005.75
9,819.11 ± 1289.20
A
16
NPRQ
0.69 ± 0.09
0.75 ± 0.11
0.79 ± 0.07*
0.80 ± 0.09
B
16
0.70 ± 0.10
0.74 ± 0.09
0.73 ± 0.07
0.81 ± 0.09
vs B *p < 0.05
Table 15.29  Changes in inflammatory mediators and cytokines in burn patients pg ml
/
, x
s
±
(
)
Group
Case number
Monitoring indexes
PBD
1
7
14
21
A
16
Prostaglandin E2
152.34 ± 17.60
48.79 ± 17.08
40.42 ± 15.19*
39.07 ± 8.63**
B
16
139.25 ± 31.65
48.88 ± 22.06
70.38 ± 25.33
44.97 ± 19.63
A
16
Thromboxane R2
801.84 ± 417.00
684.29 ± 219.80
299.12 ± 151.25*
301.10 ± 87.33**
B
16
710.75 ± 98.12
574.38 ± 259.42
366.12 ± 136.16
286.09 ± 301.46
A
16
Tumor necrosis factor ɑ
20.12 ± 8.42
19.07 ± 2.54
12.67 ± 3.48*
10.09 ± 4.29**
B
16
23.46 ± 18.22
16.48 ± 4.61
16.68 ± 7.10
13.39 ± 3.95
A
16
Interleukin-6*
587.27 ± 198.01
129.67 ± 35.28
67.35 ± 24.51*
65.74 ± 28.36**
B
16
693.62 ± 270.18
151.00 ± 81.89
94.55 ± 44.84
101.21 ± 42.38
Note: compared with group B, *p < 0.01, **p < 0.05
15.4  Growth Hormone and Metabolism

390
3. Nitrogen balance: an accumulation of nitrogen loss in
group A patients decreased from 63 to 32 g on the 21st day
after burn, while that in group B decreased from 61 to 43 g.
In a comparison of the reduced level in the two groups, the
difference was statistically significant (p < 0.05).
From the above-mentioned study, we found that rhGH
applied 7 days after the burn played a role in the regula-
tion and control of a high metabolism response after a
burn. The body, by increasing the GH, IGF-1, and insulin
levels, and lowering the plasma inflammatory mediators
and cytokines levels, achieved effective regulation and
control of the high metabolic response to burn the body, to
promote protein synthesis, accelerate wound healing, and
to improve the nutritional metabolism.
15.4.4
The Role of GH in Burn Tissue Repair
and Wound Healing [76, 86]
The Tianjin Institute of Burns, between 1996 and 1998, ran-
domly classified 22 burns patients, after obtaining informed
consent, into a GH group (n = 13) and a control group (n = 9).
The patients of the GH group were subcutaneously injected
with rhGH (0.25U/kg·day every night, continuing for
14 days. Wound tissue biopsy was carried out, before and
14 days and 28 days after drug use, for detection using flow
cytometry and immunohistochemistry.
1. Cytokeratin (CK): broad-spectrum CK antibodies can
identify almost all types of ECs. Immunohistochemical
staining of the wound biopsy by broad-spectrum CK
polyclonal antibodies and marked epithelium-derived
cells  was carried out to clearly observe the wound-­
healing, epithelial regeneration process. On day 0 two
specimens were granulation wounds, with no continu-
ous layer of ECs. We were able to see ECs of the gland
from some of the remnants of skin adnexa. Fourteen
days afterward, there were differences in the thickness
and structure of the epithelial cell layer between the
rhGH group and the control group, i.e., for the former
group, the epithelial cell layer was thicker, the basement
membrane was intact, and the papillary structures
between the dermis and the epidermis were clearer.
However, these differences were more distinct between
two groups.
2. Proliferating cell nuclear antigen: there was no PCNA-­
positive ECs in the specimen before drug use, but 14 and
28 days afterward we could see PCNA-positive cells in the
slice from the rhGH group, mainly in the germinal ECs
and spinous cells, and the closer to the basement mem-
brane they were, the more numerous they were. Positive
ECs from the rhGH group section were significantly more
numerous than in the control group and in normal skin.
3. Expression of epidermal growth factor receptor (EGFR):
the specimen consisted only of granulation tissue before
taking the medicine, and fibroblast cells with positive sig-
nals could be seen occasionally. Fourteen and 18  days
afterward, the two sections showed that the wound had
been covered by epidermis. However, the expression of
EGFR on epithelial cell membrane of the two groups was
different; in other words, the two groups were significantly
different with regard to EGFR expression. Not only was it
visibly higher in the rhGH group than in the control group,
but also positive cells showed deeper staining, which sug-
gested a greater density of cell membrane EGFR.
4. Flow cytometry (FCM): in modern times, the detection of
wound tissue in the cell PI (Table 15.30) and S-phase cell
fraction (SPF; Table 15.31) is an important indicator in
observing and evaluating the situation of cell prolifera-
tion, and detecting PI and SPF of burn wound tissue using
FCM, so as to assess a general state of cell proliferation in
the wound. From Tables 15.30 and 15.31 we can see that
there is no difference in PI and SPF between the two
groups before treatment. However, on the 14th and the
28th days, the PI and SPF of the rhGH group clearly
increased and were all markedly higher than in the control
group during the same period. This tells us that for the
rhGH group, after rhGH treatment, the wound cells that
were in the S-phase, the C1-phase, and the M-phase
increased; thus suggesting that rhGH had an impact on
the cell cycle of wound tissue cells, i.e., DNA synthesis
increased, mitosis increased, and therefore the healing of
the burn wound was promoted.
From the dynamic wound biopsy for burns patients
and the morphological observation of local wound skin,
we saw for the first time from the wound of domestic
burns patients the determinant role of GH in the process
of burned skin tissue repair: This indicates that GH can
change the proliferative activity of cells, promote DNA
synthesis, and promote differentiation and proliferation of
cells, thereby promoting wound healing. This kind of pro-
moting role is different from that of traditional methods,
and it not only provides necessary conditions for cell pro-
liferation, but also:
Table 15.30  The comparison of proliferation index (PI; %) with
wound tissue specimens
Group
n
PBD 0
PBD 14
PBD 28
GH
18
11.13 ± 0.62
21.34 ± 0.91*
16.76 ± 0.86*
Control
15
11.97 ± 0.88
12.00 ± 1.16
10.38 ± 0.59
Note: *p < 0.01
Table 15.31  The comparison of the S-phase cell fraction (SPF; %)
with wound tissue specimens
Group
n
PBD 0
PBD 14
PBD 28
GH group
18
10.24 ± 0.79
19.2 ± 0.53*
16.97 ± 0.62*
Control group
15
11.09 ± 1.20
9.87 ± 0.84
9.76 ± 0.48
Note: *p < 0.01
15  Metabolism in Burns

391
(a) Controlled the cell cycle so as to increase those cells
in the G1-phase, S-phase, and M-phase.
(b) Improve the serum concentration of growth factor;
these growth factors could serve as a second messen-
ger to play a role in promoting cell proliferation.
(c) Improve the expression of some cytokines receptors
that are in the corresponding target cell membrane.
(d) Improve the nutritional metabolism and provide
energy and raw materials for cell growth, maturity,
splitting, and other activities.
According to the clinical evaluations from the
Southwest Hospital Burn Institute of the Third
Military Medical University, the 304 Hospital Burn
Institute, the burn department of the First Affiliated
Hospital of Jiangxi Medical College, the Changhai
Hospital burn unit of the Second Military Medical
University, the Xijing Hospital burn unit of the Fourth
Military Medical University, the five units at which
rhGH is applied polycentrically, randomly, and pro-
spectively in burns treatment, rhGH was proved to
play a role in promoting protein synthesis and improv-
ing immune function. It could accelerate wound heal-
ing, not only by promoting epithelium proliferation
and migration so as to complete the repair of the
wound, but also by promoting the growth of granula-
tion tissue so as to provide the conditions for skin sur-
gery. Although the mechanism of how rhGH promotes
wound healing is still not clear, there are some simi-
larities between the process of tissue repair and the
state of normal growth. Many tissue cells such as
fibroblast cells, lymphocytes, vascular endothelial
cells, and fat cells contain the GH receptor, and the
GH can act directly on effector cells, or by stimulat-
ing the liver cells to produce IGF-1 indirectly so as to
increase DNA replication and mRNA expression.
From the three stages of wound healing, we can see
that GH plays a role in stimulating and strengthening
macrophages during the inflammatory period, stimu-
lating fibroblasts to secrete collagen during the period
of proliferation and differentiation, promoting the
growth of granulation tissue, stimulating the prolif-
eration of epidermal cells, and in collagen deposition
and collagen arrangement during the period of struc-
tural alteration. Therefore, GH plays a very important
role in inflammatory cells, repair cells, growth fac-
tors, and matrix during wound healing.
15.4.5
Effect of GH on Regulating
Metabolism and Nutrition in Burns
[83, 87]
1. The effect of rhGH in burn treatment is affirmed: from
1996 to 2004, clinical research involving 89 cases
showed us that it has a significant effect on the burns
patients with different burn areas and different ages as
long as it is used in an appropriate way, and the most
prominent aspect is to promote the wound healing. In
2002, the Southwest Hospital of the Third Military
Medical University and five other burns units applied
rhGH polycentrically, randomly, and prospectively at
0.2–0.4 U/kg·day to 200 adult patients whose burn area
was more than 20 % of the TBSA, and the results showed
that the plasma protein content in the rhGH group of
patients clearly increased, the immune function recov-
ered rapidly, the duration of wound healing was short-
ened, and the healing rate increased significantly. The
damage to the burn patients and severity is generally
decided by area and depth. During so many measure-
ments of burn treatment, how to promote wound healing
is the key technology; however, rhGH is the best and
most effective nonsurgical way of treating burns and
healing wounds. GH may regulate the proliferative activ-
ity of skin cells with the specific use of hormones, and
promote the synthesis of DNA, cell differentiation, and
proliferation so as to accelerate wound healing. This type
of role surpassed a variety of traditional methods of burn
treatment, providing a passive form of the conditions
needed for wound healing. For the first time, it takes the
initiative in achieving healing through the use of drugs;
thus, the best combination in the treatment of burn
wounds is skin graft surgery plus the application of GH,
which creates a new prospect for contemporary burn
treatment.
2. Security: as a type of method of burns treatment, how to
get the largest benefit and minimize the risk when using
rhGH is an significant problem. No adverse reactions
occurred among this group of cases in clinical studies,
because the rhGH in burn treatments was used for only a
short period. However, attention should still be paid to
three key points while using rhGH:
(a) Dosage applied: rhGH is a type of endocrine hor-
mone that stimulates the body in a dose-dependent
manner in a broad dosage. An excessive or a very low
dosage causes metabolic disorders and ineffective
treatment. The current international generic dose is
0.2–0.4 U/kg·day for the burns department, and 0.15–
0.2 U/kg·day for general surgery, with a 1- to 3-week
course of treatment, but children with GHD or IGHD
should use rhGH at 0.1 U/kg·day, which is close to
the physiological dose. We suggest that a low dosage
at 0.2  U/kg·day might be better during burn treat-
ment, because the occurrence of adverse reactions
increases dramatically when the dose is increased to
0.4–0.6 U/kg·day.
(b) Timing of application: a severe burn has a high meta-
bolic response and the stress reaction is intense. In
the early phase, the burned bodies are at a stage when
15.4  Growth Hormone and Metabolism