Dehydroepiandrosterone decreases mortality rate and improves cellular immune function during polymicrobial sepsis.

OBJECTIVE: Sepsis is associated with a marked depression of cellular immune function. The steroid hormone dehydroepiandrosterone (DHEA) is proposed to have immunoenhancing activities. We, therefore, investigated the effect of DHEA on the mortality rate and cellular immune functions in an experimental model of sepsis. DESIGN: Randomized animal study. SETTING: Level I trauma center, university research laboratory. SUBJECTS: Male NMRI mice. INTERVENTIONS: Mice were subjected to laparotomy (sham) or cecal ligation and puncture (CLP). Mice were treated with (sham/DHEA; CLP/DHEA) or without (sham; CLP) the steroid hormone DHEA (30 mg/kg sc). Animals were killed 48 hrs after the onset of sepsis. MEASUREMENTS AND MAIN RESULTS: The survival rate of septic mice was determined 24 and 48 hrs after onset of sepsis. Forty-eight hours after the septic challenge, a white blood cell count was performed and serum tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta concentrations were monitored using ELISA. Furthermore, the delayed type of hypersensitivity (DTH) reaction was evaluated on the basis of ear pinna swelling after dinitrofluorobenzene (DNFB) administration, and clinical variables (body weight, temperature, heart rate, fluid input/output, food intake) were monitored using metabolic cages. DHEA administration improved the survival rate (87% vs. 53% after 48 hrs; p <.001). This was accompanied by a restoration of the depressed DTH reaction and a reduction in TNF-alpha serum concentrations (20.7 +/- 1.4 pg/mL vs. 32.4 +/- 6.6 pg/mL). CONCLUSIONS: These results demonstrate that DHEA administration leads to an increased survival following a septic challenge. The immunoenhancing effect of DHEA is accompanied by a reduction of TNF-alpha release and an improved activity of T-cellular immunity. DHEA administration may, therefore, be beneficial in systemic inflammation.

[Optimal duration of primary surgery with regards to a "Borderline"-situation in polytrauma patients. Arbeitsgemeinschaft "Polytrauma" der Deutschen Gesellschaft für Unfallchirurgie]. / Welche primäre Operationsdauer ist hinsichtlich eines "Borderline-Zustandes" polytraumatisierter Patienten vertretbar? Eine prospektive Evaluation anhand des Traumaregisters der DGU. Arbeitsgemeinschaft "Polytrauma" der Deutschen Gesellschaft für Unfallchirurgie.

Primary stabilization of major fractures in polytrauma patients is known to represent an important principle of treatment and has been shown to reduce the incidence of posttraumatic complications and of organ failure. However, in critically injured patients it has been discussed that extensive primary definitive treatment may also cause adverse effects due to its systemic burden by blood loss, loss of temperature etc. Patients who deteriorated unexpectedly following primary surgery have been named "borderline patients". In these patients it appears necessary to limit the amount of operative procedures, e. g. by performing temporary fixation of major fractures primarily. The threshold beyond which surgical procedures may cause more harm than good has not been well defined. This holds true especially for the duration of primary surgery. We investigated the clinical outcome in a large number of prospectively documented multiple trauma patients with respect of the duration of primary fracture stabilization. If a primary surgical procedure exceeded 6 hours in multiple trauma patients with an ISS of 25 points, patients demonstrated a significantly elevated ventilation time, an increased mortality, and a higher incidence of death from MOF in comparison with patients that were injured comparably, but were submitted to shorter primary operative procedures.

Reticuloendothelial system activity and organ failure in patients with multiple injuries.

HYPOTHESIS: Reticuloendothelial system function is altered in patients with multiple trauma and organ failure. DESIGN: Prospective cohort study. SETTING: Surgical intensive care unit at a level I trauma center. PATIENTS: Patients with multiple blunt trauma and injury severity scores greater than 20, with no referrals. INTERVENTIONS: Every second day reticuloendothelial system (RES) clearance capacity and liver blood flow were determined by administering labeled human albumin. Liver function was measured by enzymatic decay of indocyanine green, and levels of plasma tumor necrosis factor alpha were evaluated. RESULTS: In nonsurviving patients with blunt trauma, RES function was altered and was associated with organ dysfunction and infectious complications. Of 61 patients, 42 survived and 19 did not. Sixteen patients (84%) died of multiple organ failure. Significantly elevated RES activity (colloid clearance rate) was present between day 5 and day 13 after trauma in nonsurvivors (0.86+/-0.16 [mean +/- SD] on day 7, P = .003) compared with survivors (0.48+/-0.08 on day 7) and 20 healthy volunteers (0.47+/-0.06); RES activity then decreased to subnormal levels in nonsurvivors. Tumor necrosis factor alpha plasma levels were elevated early after injury only in nonsurvivors (on day 1: nonsurvivors, 1.2+/-0.4 ng/mL [mean +/- SD]; survivors, 0.5+/-0.2 ng/mL; P = .02). Indocyanine green half-life values increased late after trauma, indicating late organ failure (on day 19: nonsurvivors, 111+/-29 minutes [mean +/- SD]; survivors, 12+/-4 minutes; P<.001). CONCLUSIONS: Early after trauma, nonsurviving patients demonstrated increased proinflammatory cytokine levels, followed by a state of pathological hyperactivation of the reticuloendothelial system prior to death. These results indicate that the stationary host defense system is involved in the mechanisms causing organ failure after severe trauma.