Ann. Medit. Burns Club - vol. VII - n. 2 - June 1994
IMMUNOLOGICAL PROFILE IN MAJOR BURN CASES
COMPARED WITH SURGICAL AND CLINICAL EVALUATION PARAMETERS
Cavallini M., Tesauro P, Campiglio G.L.,
Grappolini S.
Istituto di Chirurgia Plastica,
Universit& di Milano, Milan, Italy
SUMMARY. Infective
complications are the most feared in the prognosis of major burn cases. They can be
reduced by appropriate antibiotic and nutritional therapy. The onset of sepsis can also be
affected by early or late escharectomy. This study, carried out at the Plastic Surgery
Institute and Bum Centre of Niguarda Ca' Granda Hospital in Milan (Italy), reviewed a
group of bum patients. The group was monitored with regard to the immunological profile in
order to make a comparison between our data and those in the literature. Our aim was to
establish if it was possible to associate the changes in some immunological parameters
with the appearance of septic phenomena.
Sepsis is the most serious complication in
burn patients.
Adequate medical, nutritional and surgical therapeutic procedures can reduce the risk of
infection. This study reviewed 21 patients hospitalized in Niguarda Ca' Granda Burn Centre
in Milan, Italy. The patients were monitored with regard to the immunological profile in
order to make a comparison between our data and those in the literature and if possible to
associate particular variations in immunological parameters with the appearance of septic
phenomena (with a view to extrapolating some signs and predictive symptoms) also with the
use of early or late escharectomy.
Materials and methods
We examined 21 burn victims admitted
to the Reconstructive Plastic Surgery Institute and Burn Centre of Niguarda Ca' Granda
Hospital in Milan, during the period between January 1990 and August 1992. The patients
(17 males and 4 females) were between 7 and 67 years old (mean age, 37.5 years).
The mean total body surface area burned was 35.9% with a mean percentage of serious burns
of 20.6%. The characteristics of the patients are reported in Table 1.
The patients were monitored every three days until normal serological parameters were
observed, on the basis of the assessment of data concerning the Immoral immune response
(leucocytes, factor 1, complement factors, immunoglobulins, serum proteins and cortisol)
and the cellular immune response J4 and T8 lymphocytes, T4/T8 ratio).
Twice weekly we took skin samples for the antibiogram and the topogram and performed a
bacteriological examination of the tip of the urinary bougie. We also carried out, when
necessary, bronchoaspiration, urinocultures and haemocultures, as well as bacteriological
tests on the central venous catheter. From the clinical point of view, the criteria for
judging the presence of an ongoing sepsis were:
Introduction
Number |
21 |
Sex
Male |
17(81%) |
Female |
4(19%) |
Mean
age (years) |
37.5 (range,
7-67) |
Mean
weight (kg) |
69.9 ± 17.6
(range, 32-100) |
Mean
height (em) |
166.7 ±: 14.7
(range, 120-186) |
Mean
surface area (m2) |
1.78 ± 0.29
(range, 0.99-2.2) |
Mean
bum size (% TBSA) |
35.9 ± 15.5
(range, 20-90) |
Mean
full-thickness burn (% T13SA) |
20.6 ± 17.9
(range, 2-60) |
Aetiology
of burn |
|
Flame |
16(76.2%) |
Motor
car accident |
3(14.2%) |
Electric |
1(4.8%) |
Scald |
1(4.8%) |
Inhalation
injury |
5(23.8%) |
Pre-existing
illness |
|
Hypertension |
1(4.8%) |
Diabetes |
1(4.8%) |
Microcytic
anaemia |
1(4.8%) |
Asthmatic
bronchitis |
1(4.8%) |
Cardiac
arrhythinia |
1(4.8%) |
Associated
injuries |
|
Traumatic
fracture |
3(14.2%) |
Length
of stay (days) |
60.4 ± 22.9
(range, 34-138) |
|
Table 1 - Patient population |
|
- hyperpyrexia - tachycardia - hypotension - hyperventilation
- oliguresis - confusion and psychic disorientation - aggravation of tegumentary lesions.
- From the microbiological point of view, we observed ~ in
the event of sepsis - positivation of the haemocoltures.
- With regard to surgical procedures we performed 42
escharectomies, divided into two subgroups: 27 early operations (by day 7 post-burn) and
15 late operations.
Three septic episodes occurred in seven of
the patients between day 10 and day 35 post-burn (average time 19.3 days). The patients
MOSt subject to sepsis were the younger ones, with more extensive and deeper burns,
especially when the areas remained critical for longer periods. The septic episodes also
tended to occur in patients presenting previous systemic pathologies (e.g. hypertension
and asthmatic bronchitis) and who were hospitalized longer. From the aetiological point of
view (as shown by haernocultures), Staphylococcus aureus was involved in six cases
and Enterococcus and Candida in one case each.
The organisms isolated in skin samples were as follows:
- Staphylococcus aureus:
95%
- Pseudomonas auriginosa:
48%
- Enterococcus: 33.3%
- Candida albicans:
14.3%
- Enterobacter cloacae:
14.3%
- Candida parapsilosis:
4.8 %
The eight septic episodes occurred in
those patients who received time-deferred surgical therapy.
Results
We considered the results in relation
to the following
Effect of sepsis on the immune response
Comparing the average values of the two
groups of patients (septic and non-septic) at the same postburn moment, it emerged that in
the group with sepsis there was:
- an increase in leucocytes, factor I and C-reactive protein
- a decrease in albumin, fibronectin, alpha 2 macroglobulin
and T4 lymphocytes
- normal values of blood platelets, C3, C4, IgG, IgA, IgM,
total proteins, cortisol, T8 lymphocytes and T4/T8 ratio.
Analysing the non-septic group, we found:
- an increase in leucocytes, blood platelets, factor I and
C-reactive protein
- a decrease in albumin
- normal values of C3, C4, IgG, IgA, IgM, total proteins,
fibronectin, alpha 2 macroglobulin, cortisol, T4 and T8 lymphocytes and T4/78 ratio.
Humoral
function |
Unit |
Normal
range |
Haematology |
|
|
White
blood cell count (WBC) |
10
E9/1 |
4.8-10.8 |
Platelets |
10
E9/1 |
130-400 |
Coagulation |
|
|
Fibrinogen |
mgldl |
250-460 |
Complement |
|
|
C3 |
mg/dl |
83-
177 |
C4 |
mgldl |
15-45 |
Immunoglobulin |
|
|
IgG |
mg/dl |
800-1800 |
LgA |
mgMI |
90-450 |
Igm |
mg/dl |
60-280 |
Serum
protein |
|
|
Total
protein |
gmIdl |
6.4-8 |
Albumin |
gni/dl |
16-4.8 |
Fibronectin |
mgMI |
25-40 |
Alpha 2
macroglobulin |
mgMI |
150-400 |
C -
reactive protein |
mgMI |
<
0.8 |
Blood
cortisol |
pg/dl |
8-25 |
Cellular
function |
|
|
T4 |
% |
50
5 |
T8 |
% |
24
4 |
T4/T8 |
0/0 |
2.06
± 0.37 |
|
Table II - Serologic assay of immunocompetence aspects. |
|
|
Sepsis |
No
documented |
|
|
sepsis |
Number |
7 |
14 |
Sex male |
6 |
11 |
Female |
1 |
3 |
Mean age
(years)* |
31.3 (7 - 62) |
40.6 (15 - 67) |
Mean bum
size (% TI3SA)* |
48.6.t 20.6 |
29.6 ~t 6.9 |
|
(30-90) |
(20-45) |
Mean %
T13SA full-thickness burn* |
35 ± 18.5 |
13.4 --t: 13.1 |
|
(10-60) |
(2-40) |
Aetiology
of burn |
|
|
Flame |
5(71.4%) |
11(78.7%) |
Motor
car accident |
2(28.6%) |
1(7.1%) |
Electric |
|
1(7.1%) |
Scald |
|
1(7.1%) |
Inhalation
injury* |
3(42.9%) |
2(14.2%) |
Pre-existing
illness |
|
|
Hypertension |
1(14.3%) |
|
Diabetes |
|
1(7.1%) |
Microcytic
anaemia |
- |
1(7.1%) |
Asthmatic
bronchitis |
1(14.3%) |
|
Cardiac
arrhythmia |
|
1 (7.1%) |
Associated
injuries |
|
|
Traumatic
fracture* |
2(28.6%) |
1(7.1%) |
Length
of stay (days)* |
74.3 ± 32.3 |
53.5 ± 13.3 |
|
(50-138) |
(34-81) |
*P<0.005 |
|
|
|
Table III -
Characteristics of septic patients vs non septic patients |
|
Effect of early
and late surgical treatment on the immune response
Patients subjected to early escharectomy
showed:
- a significant increase in blood platelets and C4
- a decrease in fibronectin and IgM, factor I and white blood
cells, albumin, total proteins and alpha 2 macroglobulin
- no significant variations in C3, IgG, IgA, C-reactive
protein, cortisol, T4 and T8 lymphocytes and T4/T8 ratio.
Patients subjected to late escharectomy
showed:
- a significant increase in C3, C4, IgG, IgA, fibronectin and
total proteins, albumin, alpha 2 macroglobulin and T8 lymphocytes
- a decrease in IgM, C-reactive protein, white blood cells
and T4/T8 ratio
- no variations in blood platelets, factor 1, cortisol and T4
lymphocytes.
Our data indicate some conclusions that
are in contrast with data in the literature. The monitoring of the immunological profiles
of burned patients is a very difficult task, also in view of the many possible variables,
such as:
age (a favourable factor in children
under the age of two years and in elderly patients, respectively because of immaturity and
deficiency of immune reactions)
previous diseases (diabetes,
malnutrition, cardiopathologies, immune deficiencies, cortisone therapy) burn depth and
percentage type of accident (involving also respiratory system injuries due to toxic gas
inhalation)
possible concomitant injuries.
Immunological
parameter |
Unit |
Sepsis
(N = 8)
Mean |
No sepsis
(N = 14)
Mean |
Post-burn
days |
|
19.3 |
17.1 |
WBC
count |
10
E9/1 |
17213 |
13357 |
Platelets |
10
E9/1 |
292750 |
427071 |
Fibrinogen |
mg/dl |
748 |
723 |
C3 |
mg/dl |
122 |
139 |
C4 |
miz/dl |
21 |
26 |
IgG |
mg/dl |
1292 |
1289 |
lgA |
mgldl |
245 |
312 |
Igm |
mg/dl |
172 |
184 |
Total
protein |
gnVdl |
6.7 |
6.7 |
Albumin |
gmldl |
3.3 |
3.1 |
Fibronectin |
mg/dl |
26 |
29 |
Alpha 2
macroglobulin |
mgldl |
125 |
153 |
C -
reactive protein |
mgldl |
18 |
14 |
Blood
cortisol |
pg/dl |
25 |
21 |
T4 |
% |
39.6 |
48 |
T8 |
% |
__22 |
27 |
T4/T8 |
% |
1.873 |
1.943 |
|
Table IV - Immunological profiles: septic patients
vs non septic patients |
|
Immunological
parameter |
Unit |
Group 1
(early E/G)
(N 15) |
Pre-E/G
Mean |
Post-E/G
Mean |
WBC count |
10 E9/1 |
17957 |
13171 |
Platelets |
10 E9/1 |
268000 |
341857 |
Fibrinogen |
mgldl |
722 |
640 |
C3 |
mgldl |
120 |
125 |
C4 |
mgldl |
20 |
22 |
IgG |
mg/dl |
1225 |
1174 |
lgA |
mgldl |
265 |
238 |
Igm |
mg/dl |
182 |
160 |
Total protein |
gm/dl |
6.66 |
626 |
Albumin |
gn-i/dl |
3,27 |
3.08 |
Fibronectin |
mg/dl |
31.1 |
26.8 |
Alpha 2 macroglobulin |
mg/dl |
157 |
136 |
C - reactive protein |
mg/dl |
13.4 |
13 |
Blood cortisol |
1Ag/dl |
22.7 |
22.4 |
T4 |
% |
41.5 |
43.04 |
T8 |
% |
21.4 |
21.9 |
T4/T8 |
% |
2.024 |
2.106 |
|
Table V - Immunological profiles: excision and
grafting (E/G) procedures |
|
Immunological
parameter |
Unit |
Group
II (late E/C)
(N 27)
|
Pre-E/G
Mean |
Post-E/G
Mean |
WBC count |
10
E9/1 |
12189 |
9762 |
Platelets |
10
E9/1 |
344259 |
359519 |
Fibrinogen |
mg/dl |
585 |
573 |
C3 |
mgldl |
130 |
136 |
C4 |
mgldl |
27 |
30 |
IgG |
mg/dl |
1341 |
1487 |
lgA |
mg/dl |
250 |
264 |
Igm |
mg/di |
134 |
113 |
Total protein |
gmi |
6.66 |
6.85 |
Albumin |
grn/dl |
3.26 |
3.41 |
Fibronectin |
mg/dl |
35 |
40 |
Alpha 2
macroglobulin |
mg/dl |
141 |
157 |
C - reactive
protein |
mg/dl |
7.3 |
5 |
Blood cortisol |
pg/dl |
20.5 |
21 |
T4 |
% |
41.9 |
41.6 |
T8 |
% |
31.2 |
24.6 |
T4/T8 |
% |
1.525 |
1.325 |
|
Table V1 - Immunological profiles: excision and
grafting (E/G) procedures |
|
Discussion
In agreement with data in the literature
(1, 2, 3, 4, 5, 6, 7), our research shows that burned patients present a high
susceptibility to infective risks.
It is not possible to define exactly which area of immunocompetence is most involved. Many
authors (1, 8, 9, 10, 11) refer to T-lymphocytes, in consideration of the fact that their
function often changes in burns.
These observations were not however confirmed by our data, as the immunological parameters
monitored in our research gave rise to contrasting results.In accordance with the
literature, it emerged that in burned patients (septic and non-septic):
- Leucocytes showed rapid increases (to as much as twice the
normal values). Early post-burn leucocytosis generally implied high levels of B cells,
monocytes, neutrophil granulocytes and progenitor cells in immature forms. In the late
phase the main presence concerned T cells. It is also important to remember that topical
use of silver sulphadiazine and povidone iodine may contribute to change the values. These
substances cause leucocytopenia that disappears within one or two days after suspension of
topical treatment (2, 9, 11, 12, 13, 14, 15).
- Factor I initially decreased because of its conversion into
fibrin in areas where microthrombosis phenomena occurred after day 2 post-burn. It then
increased to twice the normal value and stayed at that level for many weeks
- C-reactive protein increased progressively, reaching a
plateau where it remained for many weeks. Normalization usually occurred after several
months
- Total proteins diminished after the burn trauma, and in
particular albumin decreased steadily (16, 17).
- T4 helper lymphocytes diminished (8, 14, 18).
In contrast with the results in
literature, we did not find any significant correlations with parameters that are
considered critical in the immunological balance, such as: T4/T8 ratio, fibronectin and
complement factors (with regard to this last parameter the values in our study remained
normal, without any increase).
Alpha 2 macroglobulin, a high molecular-weight protein (850 000 D) that generally
increases during the first days and then rapidly stabilizes, behaved almost normally,
remaining within the minimum values of normality.
Cortisol, which usually increases two to four times and is directly proportional to the
gravity of the patient's burns, remained within the maximum values of normality (19).
The above data make it difficult to form any systematic conclusions. The standard
behaviour of many parameters shows that the physiopathology of the burn is steady and
involves stable immunological functions.
However, our contrasting results show that it is particularly difficult to make an
accurate profile of the immunological dysfunctions of burned patients.
We also believe that immunocompetence tests cannot be globally and universally determined.
It is clear that there is no exact laboratory standardization of research methods. In the
light of our data, we are in agreement with those who believe there is a prevalent
compromission of cell immunity at the expense of uninuelear cells that could act
suppressively after burns.
On the basis of our data, we think it possible to extrapolate some predictive signs of
sepsis, as we observed that certain very clear immunological dysfunctions appear during
the aseptic phase and not before. This is a consequence of sepsis, not a cause.
To conclude, since the eight cases of sepsis occurred only in the group of patients
subjected to late surgical treatment, we have further confirmation that early escharectomy
is a fundamental therapeutic defence against the appearance of sepsis in burned patients.
RESUME. Les complications
infectieuses sont les plus redoutées dans le pronostic des cas des brûlures sévères,
et pour les réduire il faut conduire une thérapie antibiotique et nutritionnelle
appropriée. L'escarrectomie précoce ou tardive peut modifier le début de la sepsis. Les
auteurs, dans une étude effectuée au Service de Chirurgie Plastique et Centre de
Brûlés de l'Hôpital Niguarda, Milan (Italie), ont analysé l'aspect immunologique dans
un groupe de patfents brûlés pour faire une comparaison entre leurs données et celles
de la littérature. Ils se sont proposés d'établir s'il était possible d'associer les
changements de certains paramètres immunologiques avec la manifestation des phénomé,
nes septiques.
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|