Inflammatory Mediators, Infection, Sepsis, and Multiple Organ Failure After Severe Trauma Christian

Waydhas, MD;

Dieter Nast-Kolb, MD; Marianne Jochum, PhD; Arnold Trupka; Susann Hans Fritz, PhD; Karl-Heimo Duswald, MD; Leonhard Schweiberer, MD

relation of (multiple) organ failure (OF) to the release of inflammatory mediators and the incidence of infection and sepsis was studied prospectively in 100 patients with multiple trauma (injury severity score=37). Sixteen patients died of OF, 47 patients survived OF, and 37 patients had no OF. Fifteen (24%) of the patients with OF showed no signs of infection. In patients with early onset of OF (n=45), infection followed with a lag of 2 or more days. In 16 (44%) of these patients, infection led to a deterioration in organ function. With late onset of OF (n=18), infection preceded OF in nine patients. Polymorphonuclear leukocyte\p=n-\elastase, neopterin, C-reactive protein, lactate, antithrombin III, and phospholipase A discriminated significantly among the three outcome groups. Of all factors, only polymorphonuclear leukocyte\p=n-\elastase showed a difference between patients with and without infection or sepsis, respectively. These data indicate that infection might not play a crucial role in the pathogenesis of posttraumatic OF in a substantial portion of patients with trauma. Early OF, especially, seems to be mainly influenced by the direct sequelae of tissue damage and shock (eg, the release of inflammatory mediators). Since infection and sepsis did not lead to an augmented release of mediators in patients with trauma, the role of both entities remains unclear. \s=b\ The

(Arch Surg. 1992;127:460-467)

of late death after major The (multiple) organ failure (OF). uted infectious cause

severe

blunt trauma

usually attrib¬ to complications that develop in the post¬ traumatic course leading to dysfunction of the respiratory and other organ systems.1"4 Sepsis is the commonly used is

It is

denominator for the clinical presentation of the syn¬ drome. Thus, sepsis is generally regarded as the main cause of OF and late death after severe trauma. As a rule, a proven bacterial focus is mandatory in most definitions of sepsis. However, in the initial descriptions of multiple for publication October 5, 1991. From the Departments of Surgery (Drs Waydhas, Nast-Kolb, Duswald, and Schweiberer, Mr Trupka, and Ms Lenk) and Clinical Chemistry and Clinical Biochemistry (Drs Jochum and Fritz), Klinikum Innenstadt, Ludwig Maximilians-University, Munich, Germany. Reprint requests to Department of Surgery, Chirurgische Klinik und Poliklinik, Klinikum Innenstadt der Ludwig Maximilians\x=req-\

Accepted

Universit\l=a"\t,Nubaumstr 20,8000 Munich 2, Germany (Dr Waydhas).

Lenk;

OF,56 it was already pointed out that despite the unifor¬ mity of the syndrome, a variety of causes other than in¬ fection may lead to organ dysfunction. For example, a clinical picture resembling sepsis can be found in acute pancreatitis in humans. Experimental studies were able to induce a sepsislike syndrome with nonbacterial, nonendotoxic inflammatory stimuli.7'8 Thus, several authors suggested that multiple OF after trauma may be the direct consequence of mediators released during tissue damage and circulatory shock and not of infectious sequelae.910 To describe this syndrome, terms such as "whole body inflammation"11 or "nonbacteremic clinical sepsis"12 were introduced. To further elucidate the role of inflammatory mediators and infection in the development of multiple

OF, we have performed a prospective study in severely injured patients. PATIENTS AND METHODS

During the study period (1986 to 1990), traumatized patients arriving at our emergency department were examined immedi¬ ately by a member of the study team and included in the prospective study if all of the following criteria were met: (1) less

than 6 hours between accident and admission to the emergency department; (2) between 16 and 70 years of age; and (3) severe injuries of at least two body regions (head/brain, thorax, abdo¬ men, skeletal system) or three major fractures. Severe injuries included the following: (1) head— unconsciousness for more than 60 minutes or with dilated pupil(s), cerebrospinal fluid rhinorrhea or otorrhea, unstable facial bone fracture; (2) thorax more than three fractured ribs, sternum fracture, pneumothorax/ hemothorax, lung contusion, aortic rupture, cardiac tamponade, rupture of the diaphragm; (3) abdomen— hollow or parenchymal organ laceration, renal contusion or laceration; (4) skeletal system— vertebral lesion (fracture of vertebral body or arch, ligamentous injury with dislocation, spinal cord injury), pelvic fractures, fractures of the femur, tibia, and/or humérus, ampu¬ tations proximal to the toes or digits. Collection of blood samples for routine and biochemical lab¬ oratory testing as well as recording of clinical data, including di¬ agnostic and therapeutic interventions, drug and infusion ther¬ apy, Glasgow Coma Scale, and cardiopulmonary monitoring data, were started within 30 minutes after arrival of the patient in the emergency department and continued on a 6-hour basis. After 48 hours, the interval was extended to 24 hours for a pe¬ riod of 14 days. After 2 weeks, the clinical course was recorded until either transfer to a general ward or death. Biochemical measurements using commercially available test kits included polymorphonuclear leukocyte (PMN)-elastase (E.

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Merck, Darmstadt, Germany), C-reactive protein (Behringwerke, Marburg, Germany), antithrombin III (Kabi, Stockholm, Sweden), neopterin (Henning, Berlin, Germany), and phospholipase A (Boehringer, Mannheim, Germany). Testing for bacte¬ ria from the urinary tract and the bronchial system was routinely

done twice a week or when clinically indicated. Blood cultures were taken when the body temperature rose above 38.5°C. Swabs for bacterial cultures were taken from all catheter tips and from wounds when indicated. The following definitions were used. Sepsis was assumed when two signs of the following signs 1 to 3 in addition to sign 4 occurred: (1) temperature of 38.5CC or greater; (2) white blood cell count (WBC) greater than or equal to 15 x 109/L or less than or equal to 5 10'/L ; (3) thrombocytes less than or equal to 100 x 109/L or a fall of greater than or equal to 30% in 24 hours; and (4) culture-proved bacterial focus. Pneumonia was supposed when one sign of the following occurred: (1) tempera¬ signs 1 to 2 plus one sign of signs 3 to 412X107L or greater; (3) ture of 38.5°C or greater;, (2) WBC of signs positive bacterial culture; (4) abnormal roentgenographic typical of pneumonia. Urinary tract infections were considered to cause the following signs: (1) positive culture with more than 104 bacteria per milliliter; (2) temperature of 38.5°C or greater; (3) WBC of 12 X 109/L or greater. Catheter infection was considered to cause the following signs: (1) temperature of 38.5°C or greater; (2) WBC of 12 x 109/L or greater; (3) positive culture from cathe¬ ter tip. Respiratory failure was indicated by the following signs: need of mechanical ventilation and Po2/fraction of inspired ox¬ ygen of 280 mm Hg or less or positive end-expiratory pressure of 8 mm Hg or greater for at least 24 hours. Renal failure was in¬ dicated by a creatinine concentration of 177 µ /L or greater for at least 48 hours. Liver failure was indicated by a bilirubin level of 51 µ / , or greater for at least 48 hours. Disseminated intra¬ vascular coagulation was indicated by the following signs: (1) thrombocyte level of 100 x 109/L or less or a fall of 30% or more in 24 hours; (2) partial thromboplastin time of 50 seconds or more for 24 hours; (3) reptilase time of 22 seconds or more for 24 hours (similar to the test for thrombin time, but with use of the enzyme reptilase instead of heparin-independent thrombinlike thrombin.13 Gastrointestinal tract failure was indicated by endoscopically proved ulcération with bleeding or acalculous chole¬

cystitis. Multiple OF was assumed if two or more organ systems failed at the same time. Statistical testing was done with the nonparametric Wilcoxon Test for two samples and the 2 test with Yates' correction. Differences were considered significant with values less than .05 and highly significant with values less than .01. The study was carried out in accordance with the Ethical Com¬ mittee of the Ludwig Maximilians-University, Munich, Ger¬ many.

Table 1.—Incidence of Organ Failure, Infection, and Sepsis in 100 Patients With Trauma* %

Factor

63 31 32

Organ

failure Isolated

Multiple

46

Pneumonia

Urinary tract

8

infection

15

Wound infection Catheter infection

1

1

Peritonitis No infection

43

Sepsis "The is

27

occurrence

of

more

than

infectious focus in

one

a

possible.

patient

Table 2. —Incidence of Multiple Organ Failure (OF),

Infection, and Bacterial Sepsis

in Three Outcome

Groups of Patients With Trauma* Group

No. of

patients

Mean ISS

Multiple OF,

No. (%)

1

Group

2

Group

16

47

37

43

39

32

15 (94)

16

3

(34) (74) (26)

9 (24) 13 (81) 35 Infection, No. (%) 28 (76) 3 (19) 12 No infection, No. (%) 2 (5) 8 17 No. (%) (50) (36) Sepsis, survivors 1 with OF; *Group comprises nonsurvivors; group 2, and group 3, survivors without OF. Percent sign indicates percent¬

ages within each group. ISS indicates

injury severity score.

and 2 compared with group 3 (P

Inflammatory mediators, infection, sepsis, and multiple organ failure after severe trauma.

The relation of (multiple) organ failure (OF) to the release of inflammatory mediators and the incidence of infection and sepsis was studied prospecti...
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