Transaminase in Burns

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Serum Transaminase Changes in Severe Burns *

MANUEL BOCANEGRA,* * M.D., FIDEL HINOSTROZA N., M.D.,


NICHOLAS A. KEFALIDES, M.D.
From the Hosptals del Nino, Arzobispo Loayza, Dos de Mayo and the Institutes of Arthritis
and Metabolic Diseases, National Institutes of Health, Bethesda, Maryland

IT IS WELL KNOWN that in a large num- The purpose of the present study was to
ber of clinical and experimental conditions determine levels of serum GOT and GPT
accompanied by tissue necrosis, the levels in burned children and adults and to cor-
of serum glutamic oxalacetic transaminase relate these changes with those seen in the
(SGOT) and to a lesser degree of serum blister fluid. Determinaitons of these en-
glutamic pyruvic transaminase (SGPT) in- zymes in the normal skin of children were
crease. CS1 12"16 1, 18 Little is known, how- also made.
ever, about changes in these enzymes in Our data show that in children there is a
skin damage produced by burns. There are moderate increase in serum levels of both
contradictory reports with respect to some enzymes between the second and the
aspects of the problem. While Ticktin et fourth day after burning with a gradual re-
al.1- and Nickell et al.1" found no increase turn to normal by the end of the second
in SGOT in patients with burns up to 25 week. In adults, these changes were less
per cent of body surface no increase in frequent and not as marked. On the other
SGOT in patients with burns up to 25 per hand, in blister fluid of both children and
cent of body surface area, Allegra 1 noted adults, levels of GOT and GPT were well
an early rise in both SGOT and SGPT in above those observed in serum in the first
80 per cent of adults with burns from 3.0 to three hours after burning when samples
20 per cent of body surface area. In some were taken simultaneously from both
cases, a second increase was observed at sources.
the end of the first week.' No studies in
burned children have been found in the Materials and Methods
literature. Recently, Arturson 2 showed in This report includes the study of 42 pa-
rats with burns of 25 and 45 per cent of tients with burns between 10 and 70 per
body surface area that the SGOT reaches cent of body surface area.7 Patients were
maximum levels 48 hours after burning. He admitted between one and three hours
reported that the highest levels were seen after burning. Twenty-six were children, 13
in animals with more extensive burns and boys and 13 girls, aged one to 12 years.
suggested that these changes are due to Sixteen were adults, four men and 12
liver necrosis which accompanies severe women, aged 14 to 49 years. Fire was the
burns in these animals. thermal agent in 46 per cent of the children
and 88 per cent of the adults. Hot liquids
* Submitted
were responsible for the burns in the re-
for publication May 10, 1962. maining patients. Patients who in addition
* * Assistant Professor of Medicine, Facultad de
Medicina, Cayetane lieredia, Lima, Peru. to the burn had other types of tissue injury
Supported by a grant from the National In- or systemic infection were excluded from
stitute of Health, U.S.P.H.S. the study.
438
Volutme 157
Nuniber 3
SERUM TRANSAMINASE CHANGES IN SEVERE BURNS 439
Patients received shock therapy accord-
ing to methods described previously.5' 8 Ve-
nous blood was drawn on admission, at the 0o 0oo00 _ ~00 0 8-t c 00 0O
C: C cd
end of 24 and 48 hours, and then every cuzcn
o 00 o 0- o o o

other day until the eighteenth day. In nine


children and nine adults blister fluid and
blood samples were obtained simultane- 00 cN C- C- 0
- - \ t
ously during the first four days after ad- cC
N

mission. oo
g a 4 o o
o1- A
Samples of healthy skin, 3.0 mm. in
thickness, were obtained using the Brown
dermatome in 30 patients aged one to 11 cC
years. These patients were admitted to the
surgical service of the Hospital del Nino 11-1 -4
o
r-
Cq n -1
"
'I
0008-
"t rn _ _,- _

either for treatment or uncomplicated in- Cl)


14)
Cl)
1!3 C)
guinal hernias, contracture scars or with 1)
IC
U-)
0-
C)

third degree burns of more than two weeks N


I.-I
C)
:;ll
duration. The skin was immediately ;11
C)
1f0
weighed within 0.1 mg. and then was
.j CC
triturated in a tissue grinder under re- C-i
. c
Lfn ~ ~ .0
frigeration, using distilled water in a ratio 31-
'-0=
.)C)
of 1:100 with respect to sample weight. pq 0 *
t 4_ 00 to M

Specimens of serum, blister fluid and skin .1


CII)
ql)
OC)

>C)
homogenate immediately were subjected t4
tlt
o - o

to analysis. Occasionally, when specimens -Z:


.j C-4 - - -

were analyzed from one to three days after Cl)


tz.
C)
;z
they were obtained, they were kept at .114

.0 0
-4.0 C. Glutamic oxalacetic transaminase tt
CII)
-1

and glutamic pyruvic transaminase were tz.


E-q
determined according to the method de- .-X cz
M
-

C 00
C
scribed by Reitman and Frankel.13 The 1'..
141)
cn
reagents and standards used were obtained 0.-
from the Sigma Company, St. Louis. With WI
.4
P.
the above method, normal values for SGOT E-4
range between 8 and 40 U./ml.; and for o
00 E
SGPT between 5 and 35 U./ml. Using this C)
,. 0
method we obtained similar values in 30 0 0i
normal children and 29 normal adults. CC
C)
0X 4 -
Lrf, c-
C)C)
cnCs
o U
Lc) C

Results 0 * C)0
C-i C N 0000 oC t m I
0o
OC
C-I (- C

1. SGOT and SGPT in Burned Chil-


dren. The average values for GOT and * *_

101
GPT and a statistical analysis in 26 burned
children are shown in Table 1. An average
admission value of 38 U./ml. was obtained o
-._ ~I o0 0CI o0

for SGOT. However, eight patients had


P-4
values up to 63 U./ml. Subsequently, there
440 BOCANEGRA, HINOSTROZA AND KEFALIDES Annals of Surgery
March 1963
was a rise in the serum concentration of
E-4 H 0
this enzyme to a maximum average of 94
00 + _0 ce '0 e s oo- '000o
0o
0 Pq ;4; r# C- rs e -0 r 00
_0
_0 Uo oUo o
U./ml. 48 hours after burn. Then levels
vi) En P4 slowly fell to reach a normal value of 31
U./ml. by the twelfth day. No changes
were registered during the remaining pe-
a) %0 Ca-, to
0 tn
% 0 0
riod of study. In six cases (23%), a sec-
Ce
f) 0 1- r- - tn \# U) 0% 0 - ondary rise was noted by the end of the
first week after burning, maximum values
of 70 to 100 U./ml. being observed on the
eighth and tenth day; typical case is shown
Cni in Figure 1. No correlation should be estab-
lished between these values and the ther-
H
I
-
00
r,
--
U4 Lof)
_--4 -I
vo co
-4C
o6 C-I
ef) C-i
t-I
coC-oo- - mo mal agent, extent of burn or other local
H C- O . -0 Wf t4
0 \0 000
. .
%0
m
skin complications.
44 . .. . .

U) ) %0 C- C- CN 00 %0 *f-0n 00o The average admission value for SGPT


1*
cii was 23 U./ml. (Table 1). In only one of 26
"I,
'0
CA cases was a level above normal obtained
ce
0 C e '-
C- C-i C-t C- of
0
o) C--
00
oo rr-
(40 U./ml.). Subsequently, there was a
gradual rise in the serum concentration of
04

Ce
C
this enzyme until it reached its maximum
of 72 U./ml. on the fourth day. During
ao
0
the following five days the level declined
*;-- slowly and then more rapidly until it
0
NsNe el c Xel cl reached a normal value of 34 U./ml. by the
.E14 aL) "0

Ce
twelfth day. There were no variations from
Ce
0 I) If V4 -i -o0-4 0o
.0
normal during the remaining period of
C-Z
-.a
.0 study. Behavior to SGOT was observed
Hi 0%r-i oo
with SGPT in that a second rise occurred
000% 0 if) 00 00%
in 23 per cent of the patients by the end
00 '0C- t- %0 C
i C- 00
siU)

Ici
Cd of the first week (Fig. 1). Maximum values
ll-
Cd* 4,
0 C during this period ranged between 52 and
~ _1 C-I _00 00CI C-. (f) I
170 U./ml.
-
C-4 .0.0
H O When serum levels for these two en-
0D
ut Ce
.5
'O
zymes are compared, it is noted the first
of)4 U)
\0 00
w e I \0
-
four days SGOT shows a greater elevation
-- -4T-q V-- -4W-4-4
0-4

than SGPT. In subsequent days this rela-


ceaL) + o% - C-N - C-i o-I 0% 0 U)r--
cd 5)
Co
, 4z. _Q tionship is preserved until both enzymes
~C reach normal levels.
*
U) I ) U) +4 e4 N C- U)C
._
4-C
._
2. SGOT and SGPT in Burned Adults.
0.*
o
-v U %0 _1) if 4 _1 C-I _I0-0
"]00 It can be seen in Table 2 that average
values for both enzymes during the time of
o E study fell within normal limits, except for
* * a slight rise of SGOT to 50 U./ml. seen on
the second day, and the definite tendency
*S
-n C- + '0 000 C- +4 '0 00
---
**
toward high normal values noted for the
"0
SGPT between the eighth and sixteenth day
Volume 157
Number 3
SERUM TRANSAMINASE CHANGES IN SEVEIRE BIJRNS 441
180r

160k
* * G0 1 r N " %
*----- G P 1
140[
E

1201
FIG. 1. Secondary in- Un
crease in serum transa-
minases, with SGPT
Li
cn
ioc I X~~~~~~~~~~~~~i
higher than SGOT. Pa- z
tient: Female, 4 years of - 8s I-
age, Thermal agent: Hot
water; area burned: 24
per cent, 14 per cent U)
third degree. Z 6C
Hx

L
40n
At% 06-..
i- ^- -_ ~P It -__
-----------------------

--1-A-'---------- --- --- -

20

c
A() 1 2 4 6 8 10 12 14 16 18
D A Y S A F T E R B U R N

160r
*-* G0T
I G PT
1401
"A%
I I

E
I.-
120- r~~~~~~~~~
III~~~~~~~~~~~~
,, 100 I
FIG. 2. Later increase
in serum transaminases,
with SGPT higher than
SGOT. Patient: Male, 14
years of age, Thermal
w
U)
<

I
80I- I/S
I

agent: Fire; area burned: < 60


22 per cent, 1 per cent
third degree. z

H 40-%L
)F. -St .'

.1

---
-d
20 4I.-

()

A() 1 2 4 6 8 10 12 14 16 18
D A Y S A F T E R B U R N

Admission.
412 BOCANEGRA, HINOSTROZA AND KEFALIDES Annals of Surgery
March 1963
* - Serum
0- * Blister fluid

A
A
n
D U L T S C H L D R E N
240
(6)
200 \ G 0 T G P T G 0 T G P T

160 \ FIG. 3. Changes in


UN (6)
serum and blister fluid
GOT and GPT. Admis-
4
z 120 8 sion values are for sam-
(6) ples taken 1 to 3 hours
I
(6) (5) after burning.
80 \8)
z
.#

cr
40 r"
--
0---4k, 8)

I
A(1)1 2 3 4 A() 1 2 3 4 A()12 3 4 A(') 1 2 3 4

D A Y S A F T E R B U R N

* Admission.
Number of patients in a total of nine in whom it was possible to do the above determinations.

after burning. However, analysis of the high values were found, ranging between
data shows that during the first six days 60 and 76 U./ml.
after burning, in 31 per cent of the cases In five patients (31%o), a later rise of
the SGOT showed values within normal both enzymes occurred between the eighth
limits; in 44 per cent there were values up and sixteenth day after burning. The values
to 50 U./ml. and 19 per cent moderate for SGOT ranged between 46 and 120 U./
elevations ranging from 60 to 100 U./ml. ml. and for SGPT between 36 and 141
In only one patient markedly elevated U./ml.; a characteristic case is shown in
values were encountered, that reached 270 Figure 2. There was no correlation between
U./ml. 48 hours after burning. In this case, these changes and the thermal agent, ex-
despite our careful selection, it is probable tent of burn or other local skin changes.
that, because of the marked severity of the 3. Transaminases in the Blister Fluid.
skin burn, the tissue necrosis also involved Shortly after burning, and particularly be-
underlying muscle. tween the first and third hour following
A similar behavior was observed with thermal trauma, marked elevations were
SGPT. In 69 per cent of cases the values noted in the concentrations of both en-
fell within normal limits. There were slight zymes in the blister fluid (Fig. 3). In chil-
elevations in 13 per cent, with a range of dren, the average value for GOT was 146
36 to 50 U./ml.; in 19 per cent moderately U./ml. and for GPT 78 U./ml. In adults

TABLE 3. Transaminases in Healthy Skin of Children


U./Gm of Wet Tissue (30 Cases)*
Mean S.E. S.D. S.E. Range
GOT 3,399 346 1,866 245 1,150-8,000
GPT 2,050 183 986 129 650 4,600
GOT
1.7 0.1 0.53 0.07 0.89-2.8
GPT
*
Age range from 1 to 11 years.
Volume 15 7
Number 3
SERUM TRANSAMINASE CHANGES IN SEVERE BURNS 443
TABLE 4. Ratio of GOT/GPT in Blister Fluid and Healthy Skin
Children Adults
Days No. No.
Postburn Det.* Mean S.E. P Det.* Mean S.E. P
Blister Fluid Admission 6 2.01 0.36 0.580 6 2.62 0.57 0.14
1 9 2.13 0.27 0.190 8 2.37 0.34 0.06
2 5 2.85 0.30 0.001 8 2.04 0.23 0.19
4 5 2.87 0.39 0.004 9 2.64 0.38 0.02
Skin 30 1.70 0.10
* Number of patients in a total of nine in whom it was possible to do the above determinations.

the corresponding values were 224 and 93 tion of these enzymes following thermal
U./ml., respectively. These values were trauma indicates, as Allegra et al.' have
three to five times higher than those ob- suggested, that the skin may be the princi-
served in simultaneously obtained serum pal source of these enzymes and skin injury
specimens (P < 0.001). may account for the changes seen. Simi-
During subsequent hours the levels of larly, other investigators'0' 14 have shown
both the enzymes decreased rapidly until, a direct relationship between the quantity
by the end of the first 48 hours, levels com- of necrotic tissue and serum levels of trans-
comparable to those in the serum were aminases in experiments involving myo-
reached. During the remaining days of cardial or liver damage. In our burned
study, no major variations were observed. patients three facts corroborate this hy-
However, while in adults the values for pothesis: 1) The amount of GOT liberated
both enzymes in blister fluid fell within the by injury of the skin involving about 10
range considered normal for serum at the per cent of body surface area would be
end of the first 48 hours, in children the of the order of 480,000 U. in a one-year-old
levels averaged 100 U./ml. for GOT and child. In an adult with 1.70 M.2 of body
45 U./ml. for GPT. surface area and 10 per cent burn, the
4. Transaminases in Healthy Skin. The GOT liberated would be of the order of
average values of GOT and GPT concen- 1,440,000 U.* These values would corre-
trations per gram of wet tissue in normal
skin of 30 children are shown in Table 3. * GOT and GPT content of skin corresponding
The skin content for GOT was 3,399 U./ to 10 per cent body surface area was calculated
Gm. of wet tissue and for GPT 2,050 by the equation:
U./Gm. The ratio GOT/GPT in the skin (Skin GOT or GPT U./Gm. wet tissue) X (Body
was 1.7 and it is similar to that in blister surface cm.2)0.1 X (skin thickness)0.3 cm.X (Sp.
fluid during the first 48 hours after burn- Gr.) 1.037.
ing (Table 4). Skin content of GOT and GPT in U./Gm.
of wet tissue is determined as described in the
Discussion text. Body surface area was calculated according
to a nomogram based on Meeh-Du Bois formula.4
Changes in serum GOT and GPT ob- The factor 0.1 represents 10 % of body surface.
Skin thickness of 0.3 cm. represents the average
served in burned children and adults fol- thickness of specimens obtained by the Brown
low the general trend reported by Artur- dermatome. The specific gravity was determined
son in experimentally burned rats. on 10 of the above samples by measurement of
Early increase in the serum concentra- the weights and volumes.
BOCANEGRA, HINOSTROZA AND KEFALIDES Annals of Surgery
444 March 1963
spond to an injury of myocardium equiva- injury.16' While liver necrosis has been
17
lent to 13 Gm. of tissue.17 According to the reported in burned animals,2 lesions in the
ratio GOT/GPT of 1.7 found for healthy liver are not frequently encountered in
skin (Table 3) we can assume that the human burns;3 and in five of our cases
amount of GPT liberated from a 10 per dying within the first week, no liver ne-
cent burn would be approximately one-half crosis was demonstrable at autopsy.**
that of GOT. It follows, therefore, that
even though transaminase content of skin Summary
is relatively low in comparison with other Serum levels of GOT andGCPT were
normal human tissue,17 in our patients, determined in 26 children and 16 adults
with burns over 10 per cent of body surface with burns between 10 and 70 per cent of
area, one would expect liberation of large
body surface area. Simultaneous determi-
amounts of enzymes, which could explain
nations of these enzymes were made in
high levels seen in the serum. 2) Blister serum and blister fluid of patients. Trans-
fluid, immediately following thermal trau- aminase content of normal skin was deter-
ma, contains large amounts of these en-
mined in 30 children.
zymes and the ratio GOT/GPT is similar
to that observed for normal skin (Fig. 3,
In children there were early and mod-
erate increases in the serum level of both
Table 4. 3) Delayed equilibrium is estab- enzymes, with maximum values observed
lished between transaminase levels of blis-
ter fluid and serum.
between the second and fourth day after
burning. In only 25 per cent of adults were
However, it should be pointed out, that such changes noted. In about 30 per cent
changes observed in transaminase levels of of patients a secondary rise occurred by
our patients, and particularly in adults,
the end of the first week.
were not of the same degree and did not
occur as early as seen in myocardial or
Blister fluid of both children and adults
liver necrosis.10 11, 16-18 This fact could be contained higher levels of transaminases
due to 1) a delay in the equilibration of than serum during the first three hours
the protein molecules between the edema after burning. By the end of the second day
fluid accumulated around the burned area these values fell to levels similar to those
and the intravascular fluid in a manner of serum. The mechanism for this phe-
nomenon is discussed.
similar to that described for tourniquet
trauma;9 and 2) a partial loss of enzymes Transaminase content of normal human
to the outside in fluid that oozes from
skin was found to be 3,399 U./Gm. of wet
these lesions in which high content in tissue for GOT and 2,050 U. for GPT. The
transaminases is indicated by high initial ratio GOT/GPT was 1.7.
levels in blister fluid (Fig. 3). While the It is suggested that the early rise in both
evidence indicates that early increases in transaminases in serum and blister fluid are
serum enzyme levels can be attributed to
due to destruction of skin and that the late
acute damage to skin, the basis for lower increase observed in a number of patients
values in adults and for secondary rises ob- by the second week after burning is prob-
served in about 30 per cent of cases is not ably due to other factors in addition to
skin necrosis.
clear. It is possible that liver damage is
responsible for the secondary rise, since it
is characterized by predominance of SGPT ** Histologic examinations performed by Dr.
over SGOT, a pattern associated with liver Gerardo Boisset, Hospital del Nino, Lima, Peru.
Volume 157 SERUM TRANSAMINASE CHANGES IN SEVERE BURNS 445
Number 3
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