Pried M., Ben-Hur N., Weiss D. *

SUMMARY. The case is described of a patient with 90% BSA burns who 60 hours post-burn developed acute adult respiratory distress syndrome (ARDS) and eventually died. A very high level of white blood cell aggregates was observed soon after admission, reflecting a state of pulmonary leukoaggregates which are a pathophysiological component of ARDS. The early detection of impending deterioration in based on the state of leukocyte adhesiveness/aggregation in the peripheral blood is useful for the assessment of the pulmonary status of severely burned patients. This is the first. case report in which the subsequent development of ARDS was predicted before this possibility was suggested by clinical, roentgenological and biochemical evidence.

A 19-year-old man who suffereed a 90% 2nd- and 3rd-degree body surface area burn injury developed the acute adult respiratory distress syndrome (ARDS) 60 hours post-injury. During the laboratory evaluation of the patient, froM. the time of his admission, his blood was examined sequentially by the leukergy test which determines the extent of leukocyte adhesiveness and aggregation in the peripheral blood. A very high level of white blood cell aggregates was observed shortly after. his admission. This finding reflects a state of pulmonary leukoaggregates, which are a pathophysiological component of ARDS.
Early detection of impending deterioration based on the state of leukocyte adhesiveness/aggregation (LAA) in the peripheral blood can help in the assessment of the pulmonary status of severely injured patients.
In animal models of severe burn trauma the LAA state (1, 2) has shown a high correlation between positive peripheral blood findings and lung pathology (3). The test also correlates well with disease activity (4). Herein is presented the first case report in which the subsequent development of ARDS was predicted before, clinical, roentgenological and biochemical evidence existed showing the typical findings of ARDS.

A 19-year-old male suffered a 90% (2nd- and 3rd-degree) BSA burr! injury, with no evidence of smoke inhalation. Fluid resuscitation was begun. Escharotomy was performed over the areas of 3rd-degree burn, and silver sulphadiazine cream was used to cover all the burned areas. The patient was haemodynamicaly stable, in full consciousness and with spontaneous breathing.
Laboratory data were remarkable for the following values: WBC 42,000/mm, H13 11.9 g/dl; Ph 7.31; Pa02 105; PaC02 36.6; HC03 18.5; 02 saturation 98%.
The chest X-ray was normal. The LAA values revealed that 45% of the patient's peripheral leukocytes were clustered in aggregates (the normal value is from 3 to 5%) (2, 5, 6). The test was performed every 12 h and showed consistently high levels of peripheral leukoaggregates.
Sixty hours after. admission the patient's condition deteriorated. He became obtunded, tachypnoeic (breath 45/min), and with signs of h4emodynamic instability. Laboratory assessment revealed WBC 22 '000/inin 3 , arterial blood gas analysis was (P02 50%) PH 7.19, Pa02 56, PaC02 59, HC03 23, 02 saturation 81%.
Chest X-ray revealed mild bilateral pulmonary infiltrates. At this time the patient was intubated and mechanical ventilatory support was given (PEEP of 8 cm H20, Fi02 of 40%). There was no evidence of sepsis, as repeated blood and tissue cultures were negative. The LAA state showed values of 4Q-50% during the entire period of hospitalization.
Seventeen days after admission the patient died in a state of cardiopulmonary arrest. Lung biopsy taken soon after , death revealed multiple leukoaggregates in the lung vasculature.

Fig. I Values of I , eukocyte, adhesiveness/aggregation in the peripheral blood during hospitalization Fig. 2 Values of W.BC count during hospitalization Fig. 3 Values of PaO 2 and PaCO 2 during hospitalization Fig. 4 Aggregates of peripheral blood leukocytes shortly after. admission Fig. 5 Magnification of W.BC aggregate Fig. 6 Presence of plugged vessel by WBC aggregate in the patient's lung

Discussion

We have observed that a rapid rise in the LAA percentage to a level ten times higher than normal in most cases indicates the presence of leukoaggregates obstructing the pulmonary vasculature.
A similar pathology was found in this severely burned patient. As expected, a considerable elevation of the LAA percentage accurately predicted impending respiratory failure at a time when the patient was clinically still stable.
The LAA state remained constantly high during the course of the disease and reliably reflected the patient's status. However, the white blood cell count declined, and the patient was stable under ventilatory support. The test is simple, sensitive and can be carried out rapidly (4-7).
The relationship between the presence of pulmonary leukoemboli and ARDS has been well documented in the literature, and this phenomenon is an important pathological component in the evolution of the syndrome (8-12). Several studies have shown that ARDS can develop in neutropenic patients (12-13). This finding is consistent with the generally accepted theory that leukoaggregates plugging the lung vasculature represent only one aspect of the pathophysio logical picture of ARDS.
Obviously our procedure will be of limited usefulness in the monitoring of such patients. The rapid rise in the level of leukoaggregates in the peripheral blood following severe trauma is due to the development of "stickiness" between white blood cells. This same process causes the white blood cells to adhere to the endothelium.
The "stickiness" develops as a consequence of the presence of various mediators in the blood stream during the early post-traumatic period. These mediators (C5a, LT134, IL-1, TNF-, GM-, CSF) (14-17) are considered to be potent leukoaggregators. On the other hand the exposure of specific 4migenic components on the surface. of the leukocyte also serves as a crucial step in the cell-cell interaction (18-22).

RESUME. Les Auteurs pr6sentent le cas d'un patient avec brillures en 90% de la surface, corporelle qui a contract6 la syndrome de d6tresse respiratoire aigu6 de I'adulte (SDRA) 60 heures apres la br6lure~ a la fin it est mort. Peu apres I'hospitalisation its ont observ6 un taux tres 6lev& des agr6gats des leucocytes, cc qui incliquait une condition de leucoagr&gats pulmonaires qui sont une composante pathophysiologiclue de la SDRA. La d6tection pr6coce d'une deterioration imminente bas6e sur la condition de I'adh6sion/agr6gation leucocytaire dans le sang p&riph&rique est utile pour 1'evaluation de 1'6tat pulmonaire des grands br6l6s. C'est le premier cas ou 1'&volution successive en SDRA a 6t& prevue avant que cette possibilit6 ne soit sugg6r6e par les 6vidences clinique, roentgenologique et biochiniique.

1. Berliner S., Sclarovsky S., Lavie G. et al.: The leukergy test in rheumatological diseases. New implications for an old test. Arth. Rheum., 28: 899-903, 1985.
2. Berliner S., Fishelson Z_ Bruchis S. et al.: The phenomenon of leukergy: Induction and detection of leukocyte aggregation in whole human blood. J. Lab. Clin. Med., 109: 575-582, 1987.
3. Fried M., Berliner S_ Ben-Hur N. et al.: Early detection of inflammation by means of leukocyte adhesiveness/aggregation: a model of burn in mice. Submitted for publication.
4. Berliner S., Fried M., Caspi D. et al.: Evaluation of disease activity in rheumatic patients by use of the state of leukoeyte adhesiveness/aggregation. Arm. Rheum. Dis., 47: 458-462, 1988.
5. Berliner S_ Caspi D., Neuman Y. et al.: Aggregation of white cells and C-reactive protein: Relation between these two indices in acute phase reaction. J. Clin. Pathol., 40: 103-106, 1987.
6. Berliner S., Fucks J., Seligsohn U. et al.: Possible role of fibrinogen in the aggregation of white blood cells. Thrombosis and hemostasis, 58: 749-752, 1987.
7. Berliner S., Sclarcivsky S_ Lavie G. et al.: The leukergy test with ischemic heart diseases. Am. Heart. J., 111: 19-22, 1986.
8. Editorial: Neutrophils and adult respiratory distress syndrome. Lancet, 2: 790-791, 1984.
9. Rinaldo J.E.: Mediation of ARDS by leukocytes. Chest, 89: 590-593, 1986.
10. Powe I.E., Short A., Sibbald W.J. et al.: Pulmonary accumulation of polymorphonuclear leukocyte in the adult respiratory distress syndrome. Crit. Care. Med., 10: 712-718, 1987.
11. Weiland J.E., Davis W.B., Hotter J.F. et al.: Lung neutrophils in the adult respiratory distress syndrome. Am. Rev. Res. Dis., 133: 218-225~ 1986.
12. Laufe M.D., Simon R.W., Flint A. et al.: Adult respiratory distress syndrome in neutropenic patients. Am. J. Med., 80: 1022-1026, 1986.
13. Maunder F.J., Hackman R.C., Riff El et al.: Occurrence of the adult respiratory distress syndrome in neutropenic patients. Am. Rev. Res. Dis., 133: 313-316, 1986.
14. Duchateu M., Haas H., Schreyen L. et al.: Complement activation in patients at risk of developing the adult respiratory distress syndrome. Am. Rev. Res. Dis., 130: 1058-1064, 1984.
15. Moore F.D., Davis C., Rodrick M. et al.: Neutrophil , activation in thermal injury, as assessed by increased expression of complement receptors. N. Eng. J. Med., 3 14: 948-953. 1986.
16. Arber N., Aronson M., Berliner S. et al.: Increased leukocvte adhesiveness/aggregation (LAA) in mice treated with recombinant granulocyte-macrophage colony stimulating factors (RGM-CSF). Blood, 72: suppl. 1-108a, 1988.
17. Pohlman T.H., Stanness K.A., Beatty P.G. et al.: An endothelial cell surface factor(s) induced in vitro by lipopolysaccharide, interleukin 1, and tumor necrosis factor increases neutrophil adherence by a CDW 18-dependent mechanism. J. Immunol., 136: 4548-4553, 1986.
18. Bevilacqua M.P., Pober J.S., Mendrick D.L. et al.: Identification of an inducible endothelial-leukocyte adhesion molecule. Proc. Nat. Acad. Sci. USA., 84: 9238-9242, 1987.
19. Schwartz B.R., Harlan J.M.: Neutrophil membrane sulfhydryl groups are involved in stimulated neutrophils' adherence to endothelium. J. of Leukocyte Biol., 45: 177-189~ 1989.
20. Zimmerman G.A., McIntyre Y.M.: Neutrophil adherence to human endotheliurn in vitro occurs by CDW 18 (Mol, MAC-I/LFAl/GP 150, 95) g I ycoprotein -dependent and independent mechanisms. J. Clin. Invest., 81: 531-537, 1988.
21. L.,Yarbrough W.C. Jr., Mason C.M., Brite W.M. et al.: Increased expression of the adhesive glycoprotein CD I I on polymorphonuclear leukocytes in adult respiratory distress syndrome. Am. Rev. Pes. Dis., 139: A221 (Abstract), 1989.
22. Osborn L.: Leukocyte adhesion to endothelium in inflammation.'Cell, 62: 3-6, 1990.