The effect of a selenium supplementation on the outcome of patients with severe systemic inflammation, burn and trauma.

Patients with systemic inflammatory response syndrome (SIRS) and sepsis exhibit decreased plasma selenium and glutathione peroxidase activity. This has been shown in several clinical studies. Moreover, the degree of selenium deficiency correlates with the severity of the disease and the incidence of mortality. Patients with SIRS and sepsis are exposed to severe oxidative stress. Selenoenzymes play a major role in protecting cells against peroxidation, especially lipid peroxidation and are involved in the regulation of inflammatory processes. Therefore, selenium substitution in those patients might be effective in the prevention of multiorgan failure. The results of randomised clinical trials investigating selenium substitution in critical ill patients with inflammation are reviewed. In two independently performed randomised, prospective clinical trials, including patients with systemic inflammatory response syndrome or sepsis, the supplementation of selenium revealed a significant reduction in multiorgan failure and, especially, a lower incidence of acute renal failure and respiratory distress syndrome. One of those trials also could demonstrate a significant reduction of mortality in the most severely ill patients. Two other studies, where selenium together with other trace elements or a mixture of antioxidants were used in the treatment of patients with severe burn injuries or trauma showed a significant reduction in the secondary infection rate, including sepsis. Thus, selenium supplementation seems to improve the outcome of patients with SIRS, sepsis and severe injury, however, pivotal prospective clinical trials with sufficient statistical power are now necessary to finally prove the efficacy of a selenium supplementation in these diseases.

[Selenium administration in sepsis patients]. / Selensubstitution bei Sepsispatienten.

BACKGROUND: It has been hypothesized that low serum selenium concentrations, associated with low glutathione peroxidase activities in critical ill patients may contribute to decreased cleavage from free radicals and deteriorate the clinical outcome. PATIENTS AND METHODS: We therefore performed a controlled, prospective study including 42 patients with inflammatory response syndrome and an APACHE-II score > or = 15. Whereas the controls (Se-, n = 21) received 35 micrograms sodium selenite during the whole treatment period the selenium substitution group (Se+, n = 21) received additional 500 micrograms, 250 micrograms and 125 micrograms sodium selenite, each amount for 3 days. Clinical outcome was monitored by APACHE-III score, documentation of acute renal failure, respiratory insufficiency and the mortality rate until discharge from the hospital. RESULTS: The mean APACHE-II(III) score on admission was 20.6 (68.3) in the Se- versus 20.1 (61.0) in the Se+ group. Age, sex, underlying diseases, the serum selenium levels and glutathione peroxidase activities on admission were equally distributed in both groups. Selenium substitution was followed by a significant increase in serum selenium levels and glutathione peroxidase activity to normal levels, whereas in controls both parameters remained low. The APACHE-III score significantly improved on day 7 (p = 0.018) and 14 (p = 0.041) in the Se+ group. Hemodialysis because of acute renal failure was necessary in 9 (Se-) versus 3 (Se +) patients (p < 0.04). Overall mortality rate in the Se+ group was 33.5% versus 55% in the Se- group (p = 0.13). A subanalysis of those patients with an APACHE-II score > 20 (n = 10) in each group revealed a significant reduction in mortality from 70% to 30% (p = 0.013). No negative side effects of selenium were seen. CONCLUSION: Selenium substitution significantly improves clinical outcome and reduces the incidence of acute renal failure.

Cyclic plasma IL-6 levels during normal menstrual cycle.

Steroid hormones including sex hormones are known to influence cytokine production by cells in vitro. We investigated whether there are differences in cytokine production in vivo and ex vivo during the menstrual cycle in five ovulating women compared with five pregnant women and nine males. Interleukin 6 (IL-6) in plasma changed periodically during 12 of 13 cycles in five women. The IL-6 levels were lowest in the luteal phase when progesterone levels were elevated and highest preovulatory when progesterone levels were low (P < 0.009). This phenomenon was unrelated to changes in haematocrit or albumin and independent of cortisone, growth hormone, luteinizing or follicle stimulating hormone and testosterone. In contrast to IL-6, the soluble IL-6 receptor did not vary significantly during the menstrual cycle. In comparison, nine males and five pregnant women had low plasma IL-6 levels comparable with women during the luteal phase. In addition, levels of IL-6, IL-10 and TNF were determined after whole blood stimulation with lipopolysaccharide ex vivo during a menstrual cycle. Neither the number of CD-14++ or CD14/CD16+ cells nor the amounts of IL-6, IL-10 and TNF after stimulation showed cyclic changes. We suggest that sex hormones, especially oestrogen and progesterone, may influence immune responses by decreasing basal IL-6 levels in vivo.

Selenium replacement in patients with severe systemic inflammatory response syndrome improves clinical outcome.

OBJECTIVE: To determine the effect of selenium replacement on morbidity and mortality in patients with systemic inflammatory response syndrome (SIRS). DESIGN: Controlled, randomized prospective open-label pilot study comparing patients with and without selenium replacement. SETTING: Intensive care unit of a university hospital for internal medicine. PATIENTS: Forty-two patients with SIRS caused by infection and a minimal Acute Physiology and Chronic Health Evaluation (APACHE) II score of 15 points on the day of admission were included. The selenium replacement group of patients (Se+; n = 21) received sodium selenite for 9 days (535 microg [6.77 micromol] for 3 days, 285 microg [3.61 micromol] for 3 days, and 155 microg [1.96 micromol] for 3 days) and thereafter, 35 microg (0.44 micromol) per day iv. The control group (Se-, n = 21) received 35 microg of sodium selenite throughout the total treatment period. INTERVENTIONS: Morbidity and clinical outcome was monitored by scoring using the APACHE III score, occurrence of acute renal failure, need and length of mechanical ventilation, and hospital mortality. Blood samples on days 0, 3, 7, and 14 were analyzed for serum selenium concentration and glutathione peroxidase (GSH-Px) activity. MEASUREMENTS AND MAIN RESULTS: The median APACHE II score at admission, age, gender, underlying diseases, serum selenium levels, and GSH-Px activities at admission were identical in both groups. In Se+ patients, serum selenium levels and GSH-Px activity normalized within 3 days, whereas in controls, both variables remained significantly low (p < .0001). The APACHE III score decreased significantly in both groups but was significantly lower in the Se+ group (day 3, p > .05; day 7, p = .018; and day 14, p = .045 Se+ compared with Se-). Hemodialysis with continuous veno-venous hemodialysis because of acute renal failure was necessary in nine Se- compared with three Se+ patients (p = .035). Overall mortality in the Se- group was 52% vs. 33.5% in the Se+ group (p = .13). CONCLUSIONS: Selenium replacement in patients with SIRS seems to improve clinical outcome and to reduce the incidence of acute renal failure requiring hemodialysis.