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

  1. 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

  1. 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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