C1 inhibitor prevents capillary leakage after thermal trauma.

OBJECTIVE: In burned patients, activation of the complement and clotting systems is suggested to play an important role in the development of the capillary leak syndrome and inflammatory tissue destruction. In an animal model of thermal trauma, the possible protective effect of C1 inhibitor (C1Inh), a major control protein of both the complement and clotting systems, was investigated. DESIGN: Prospective, controlled study. SETTING: Animal model. SUBJECTS: Healthy pigs weighing 30 kg. INTERVENTIONS: Pigs were scalded for 25 secs with 75 degrees C hot water to achieve a 30% total body surface deep partial-thickness burn. The treatment group (n = 8) received C1Inh concentrate at an initial dose of 100 units/kg body weight immediately after thermal trauma, followed by three further applications every 12 hrs. Two control groups included animals that were either scalded (n = 8) or not scalded (n = 7) and treated with lactated Ringer's solution. MEASUREMENTS: Before and at various time points after trauma blood samples were analyzed for complement activation (APH50, CH50, SC5b-9, C3). Continuous monitoring of hemodynamic variables was performed and postmortem histologic examination of specimens from lung, heart, liver, kidney, stomach, duodenum, jejunum, ileum, and colon was carried out. Aseptically collected mesenteric lymph nodes were pooled and screened for bacterial translocation. For evaluation of the burn wound, biopsies from defined scalded and not scalded areas were taken daily. As a measure for edema formation, the weight of the animals was recorded every 2 hrs. RESULTS: After C1Inh treatment, which led to a significantly reduced complement activation, the clinical outcome was clearly improved, as indicated by vital signs and as demonstrated by reduced edema formation. Treated animals presented a diminished bacterial translocation. Pathologic alterations were clearly diminished in the burned skin, in shock-related organs, and in the intestines. CONCLUSION: Application of C1Inh appears to be an effective means to prevent capillary leakage and inflammatory tissue destruction after thermal trauma.

Long-term measurements of energy expenditure in severe burn injury.

The objective of this study was to evaluate resting energy expenditure (REE) in spontaneously breathing and artificially ventilated burn patients during the entire intensive care period. In 27 patients with 51 +/- 20% body surface area burned (BSAB) the REE was determined via indirect calorimetry. Three groups were formed according to the mortality prognosis index of Zawacki et al. In groups A, B, and C the predicted mortality rates were <20%, 20% to 80%, and >80%, respectively. The frequency of acute respiratory distress syndrome (ARDS), sepsis, renal failure, and mortality increased from group A toward group C. The REE test revealed wide individual variation and was usually overestimated by all tested formulas. The mean REE was comparable in groups A, B, and C during the first 20 days (49 +/- 16% vs. 59 +/- 21% vs. 57 +/- 18% above the REE calculated by the Harris-Benedict equation, or HBEE). The REE of patients in groups A and B declined after this period, whereas the long-term ventilated patients in the prognostically unfavorable group C showed a high REE up to the 45th day, usually accompanied by severe organ dysfunction and major metabolic disorders. During this time a nutritional regimen meeting the actual REE could not be achieved. In the clinical situation when indirect calorimetry is not available, REE can be stated to be 50% to 60% above HBEE in patients with >20% BSAB for at least 20 days. Expecting a stable clinical course in patients with a predicted mortality of <20% (group A), oral nutrition usually seems sufficient after a short period of artificial nutritional support (1 week). Patients with a predicted mortality of more than 20% have a complication-burdened clinical course and a prolonged period of ventilation (groups B and C). These patients need parenteral and enteral nutrition for at least 20 days after trauma to prevent severe malnutrition.

The therapeutic effect of C1-inhibitor on gut-derived bacterial translocation after thermal injury.

To test the effects of C1-esterase inhibitor in scald burns on bacterial translocation and intestinal damage, standardized deep partial-thickness burns were inflicted on domestic pigs, scalding 30% of the skin surface for 25 s with 75 degrees C hot water. The animals (n = 17; weight 25-35 kg) were divided into three groups: I) the control group (n = 5) without scald burn; II) the group (n = 6) with scald burn; and III) the group with C1-inhibitor (n = 6): scald burn and treatment with C1-inhibitor (C1-INH; BERINERT, Behring, Marburg, Germany). Parameters measured and compared in this model were activity of complement system, hemodynamics, body weight, pathological organ alterations including intestinal lesions, bacterial translocation, and skin damage. C1-INH administration significantly decreased the plasma levels of the specific soluble membrane attack complex (SC5b-9), bacterial translocation, and the degree of intestinal ischemia in the postburn period compared with untreated animals. Moreover, animals treated with C1-INH exhibited a minor degree of organ alterations including damage of the skin and development of edema. The favorable effects of C1-INH may be explained by the protection of the intestinal and dermal microcirculation in the acute phase of thermal injury.

Procalcitonin--a sepsis parameter in severe burn injuries.

Procalcitonin (PCT) levels increase in patients with systemic infections; the highest levels have been found in sepsis. This study tested whether plasma procalcitonin level was related to sepsis, CRP, burn size, inhalation injury or mortality in severely burned patients over the entire clinical course. In 27 patients with 51 (20-91)% TBSA, PCT was measured three times weekly from admission over the entire course of stay in a single ICU. Daily scoring by the "Baltimore Sepsis Scale" was performed. The patients were assigned to three groups depending on the clinical course and outcome: A = no septic complications, B = septic complications-survivors, C = septic complications non-survivors. PCT levels were elevated slightly at admission (mean 2.1 ng/ml) except in three patients who suffered electrical burns (mean 15.7 ng/ml). PCT peak levels correlated well with the Scoring values (r = 0.84) while CRP did not (r = 0.64). Peak PCT levels were significantly higher (p < 0.005) in septic patients (B and C) who averaged 49.8+/-76.9 ng/ml, than in non-septic patients (A) who averaged peak levels of 2.3+/-3.7 ng/ml. The highest PCT levels were found immediately before death (86.8+/-97 ng/ml). Seven patients had an inhalation injury 3rd degree. In these patients at 24 h postburn, there was no relationship between PCT levels and inhalation injury but during the later days postburn there were significant differences in PCT levels in patients with versus without inhalation injury. All patients with inhalation injury 3rd degree developed septic complications. There was no positive correlation between the PCT-admission-levels and the TBSA, but there was a positive correlation between the TBSA and the mean peak PCT levels during the later days postburn (r = 0.73; p < 0.05). The cut-off value of 3 ng/ ml we found reliable to indicate severe bacterial or fungal infection. PCT values over 10 ng/ml increasing over the following days were found only in life-threatening situations due to systemic infections. The individual course of PCT in one patient is more important than absolute values. PCT presented in this study as a useful diagnostic parameter in severely burned patients.