Trauma and thermal injury: comparison of hemostatic and cytokine changes in the acute phase of injury.

BACKGROUND: Initiated either by thermal injury or mechanical trauma, the systemic inflammatory response syndrome stimulates activation of coagulation and fibrinolysis, evolving into a subclinical disseminated intravascular coagulation. METHOD: Hemostatic parameters, interleukin-6, and endothelin plasma levels were compared in burn and trauma patients. Nineteen patients with major burn injury (> or = 40% total body surface area) were compared with 35 trauma patients with Injury Severity Scores > 25 on day 1 and days 5 to 8. RESULTS: Thrombin-antithrombin levels were significantly higher in trauma patients than in burn patients (p < 0.0001) on day 1, and endothelin was significantly higher on days 1 and 5 (p < 0.0001) in trauma patients than in burn patients. Interleukin-6 plasminogen activator inhibitor-1, and tissue plasminogen activator levels were elevated above normal limits on both days in both groups. CONCLUSION: There was a difference in the degree and level to which homeostasis was perturbed between the two groups. The mechanism of injury did not affect the initiation of subclinical disseminated intravascular coagulation and cytokine release, and the physiologic response remained the same.

Postburn edema and related changes in interleukin-2, leukocytes, platelet activation, endothelin-1, and C1 esterase inhibitor.

Interleukin-2 (IL-2) promotes multisystem organ edema, lung neutrophil sequestration, and platelet activation through alterations in the microvascular barriers and permeability. IL-2, complement, platelet, and vascular endothelial activation were evaluated in 60 patients. One-factor analysis of variance indicated a significantly increased absolute neutrophil count on day 1 (p < 0.0001) and decreased C1Inh, p = 0.0001, with elevated IL-2 levels in the 20% to 40% group (p = 0.008). Endothelin-1 levels were significantly increased in the 20% to 40% total body surface area group on day 5. The absolute neutrophil count was significantly reduced in both groups, and C1Inh rose to near normal levels by day 5. No significant elevations of 6-keto prostaglandin F1 alpha were observed on day 1 or day 5 in the < 40% total body surface area group; however, these levels were significantly elevated on day 1 in the > 40% total body surface area group. Thromboxane B2 and platelet factor 4 were significantly elevated in all groups (p = 0.001) on days 1 and 5. Regression analysis implicated infection as a significant contributor to the IL-2 variations (r2 = 0.61), with inhalation injury minimally affecting IL-2 plasma levels (r2 = 0.09). Generalized edema increased with increasing burn wound size in parallel with elevated IL-2 and endothelin-1 levels, reduced C1Inh levels, and leukocytosis in the first week after thermal injury. These data suggest that there are dynamic interactions among the endothelium, cytokine stimulation, leukocytosis, complement, and platelet activation in promoting the microvascular permeability.

Burn-induced nitric oxide release in humans.

Nitric oxide (NO) generation in a series of 20 burn patients was studied with a novel anion exchange high-performance liquid chromatographic method for the simultaneous determination of nitrite (NO2-) and nitrate (NO3-), the stable metabolic endproducts of NO. The NO values within our survivor group (n = 17) were significantly altered at days 1, 6, and 12 postburn in contrast to controls (n = 23) (p < or = 0.03). NO2- values were significantly depressed in both plasma and urine, whereas NO3- values were significantly elevated in contrast to control values (p < or = 0.03). The ratio of NO2-:NO3- was significantly lower for burn patients versus controls in both plasma and urine (p < 0.01). The NO generation seemed in part to be dependent on the percentage of total body surface area burn, most dramatically elevated in patients with burns of 10 to 40% total body surface area. In subjects who did not survive beyond 36 hours postinjury because of irreversible shock (n = 3), the production of NO was significantly depressed in contrast to survivors and controls (p < 0.0001). However, the NO2-:NO3- ratio (0.001) was relatively unchanged, with reflection of a global depression in NO formation with no change in the individual component release. Burn injury resulted in an increased release/production of NO that in the first postburn week is maximally elevated immediately postinjury. NO release, although decreased at day 6 relative to the day 1 values, remained elevated into the second week postinjury when there was evidence for a further increase in NO production. The enhanced NO3- formation may well result from NO reacting with oxygen-free radicals counteracting superoxide anion-induced destruction of tissue, thereby potentially functioning as a protectant molecule.

Interleukin-2 and interleukin-6 in relation to burn wound size in the acute phase of thermal injury.

Thermal injury induces significant physiologic responses of acute inflammation, acute phase reaction and cell repair and growth, mediated by interleukins, cytokines and growth factors. To determine the relative role of interleukin-2 (IL-2) and interleukin-6 (IL-6) in the acute phase of thermal injury, 60 patients (47 men and 13 women, with average age of 37 years [1.5 to 70.0 years]) were analyzed within the first 36 hours and at five to seven days postoperatively. The patient population was categorized by percent burn (2 or 3, or both, degrees): less than 20 percent, n = 22; 20 to 40 percent, n = 18, and greater than 40 percent, n = 20. The average percent burn was 32 percent (range 4 to 95 percent). The mechanism of injury was by flame (25 instances), explosion and flame (19 instances), scald (12 instances), electric (three instances) or chemical (one instance). Twelve patients had an associated inhalation injury; 14 patients had sepsis syndrome. The overall mortality rate was 13 percent. Within 36 hours of onset of injury, IL-6 and IL-2 levels increased in proportion to the severity of the burn wound size. IL-2 levels were significantly elevated in the 20 to 40 percent burn group as compared with the greater than 40 percent group and patients in a control group (p < 0.0001). IL-6 levels increased with burn wound size and were significant only in the greater than 40 percent group (p < 0.0007). Any physiologic modulation of the thermal injury by biologic modifiers must be adapted to the extent of burn wound size and phase of injury: acute, recovery or reparative for optimal benefit and results.

The effect of burn wound size on hemostasis: a correlation of the hemostatic changes to the clinical state.

The effect of burn wound size on the activation of fibrinolysis, coagulation, and contact factors was analyzed in 60 thermal injury patients. Blood samples from 47 male patients and 13 female patients, (average age 37 years; range 1.5-70 years) were collected within the first 36 hours and at 5-7 days following injury. The patient population was categorized by percentage of burn (second degree and/or third degree): less than 20%, n = 22; 20%-40%, n = 18; greater than 40%, n = 20. The average percentage of burn was 32% (range, 4%-95%). The mechanism of injury was by flame (25), explosion and flame (19), scald (12), electric (3), or chemicals (1). An associated inhalation injury was present in 12 patients. The overall mortality rate was 13% (8). Sepsis or serious infection occurred in 23% (14) of the patients. On admission, 83% of the patients had normal prothrombin times (PT) and activated partial thromboplastin times (APTT). However, specific hemostatic variables showed marked changes. Admission hemostatic markers that correlated with the severity of injury were: tissue-plasminogen activator (tPA), plasminogen activator inhibitor (PAI), D-dimer (D-di), plasminogen (Plg), proteins C and S (PrC and PrS), antithrombin III (ATIII), thrombin-antithrombin complex (TAT), kallikrein (Kal:c), kinin (Kin), C1 esterase inhibitor (C1Inh), and factor VII clotting and antigen (FVII:c, FVII:ag). These data suggest that during the early course following burn injury, thrombogenicity is increased (TAT increases) because of a decrease in ATIII, PrC, and PrS; and fibrinolysis activation (D-di increases) occurs via an increase in tPA with a p value increase in PAI.(ABSTRACT TRUNCATED AT 250 WORDS)