Sepsis is associated with an increase in reactive oxygen species and low endogenous antioxidative capacity. We postulated that high-dose supplementation of sodium-selenite would improve the outcome of patients with severe sepsis and septic shock. Prospective randomized, placebo-controlled, multiple-center trial. Eleven intensive care units in Germany. Patients were 249 patients with severe systemic inflammatory response syndrome, sepsis, and septic shock and an Acute Physiology and Chronic Health Evaluation (APACHE) III score >70. Patients received 1000 μg of sodium-selenite as a 30-min bolus injection, followed by 14 daily continuous infusions of 1000 μg intravenously, or placebo. The primary end point was 28-day mortality; secondary end points were survival time and clinical course of APACHE III and logistic organ dysfunction system scores. In addition, selenium levels in serum, whole blood, and urine as well as serum gluthation-peroxidase-3 activity were measured. From 249 patients included, 11 patients had to be excluded. The intention-to-treat analysis of the remaining 238 patients revealed a mortality rate of 50.0% in the placebo group and 39.7% in the selenium-treated group (p = .109; odds ratio, 0.66; confidence interval, 0.39–1.1). A further 49 patients had to be excluded before the final analysis because of severe violations of the study protocol. In the remaining 92 patients of the study group, the 28-day mortality rate was significantly reduced to 42.4% compared with 56.7% in 97 patients of the placebo group (p = .049, odds ratio, 0.56; confidence interval, 0.32–1.00). In predefined subgroup analyses, the mortality rate was significantly reduced in patients with septic shock with disseminated intravascular coagulation (n = 82, p = .018) as well as in the most critically ill patients with an APACHE III score ≥102 (>75% quartile, n = 54, p = .040) or in patients with more than three organ dysfunctions (n = 83, p = .039). Whole blood selenium concentrations and glutathione peroxidase-3 activity were within the upper normal range during selenium treatment, whereas they remained significantly low in the placebo group. There were no side effects observed due to high-dose sodium-selenite treatment. The adjuvant treatment of patients with high-dose sodium-selenite reduces mortality rate in patients with severe sepsis or septic shock.

Sepsis is defined as life-threatening organ dysfunction caused by the dysregulated host response to infection. Despite serious mortality and morbidity, no sepsis-specific drugs exist. Endotoxemia is often used to model the hyperinflammation associated with early sepsis. This model classically uses lipopolysaccharide (LPS) from Gram-negative pathogens to activate the immune system, leading to hyperinflammation, microcirculatory disturbances and death. Other toxins may also be used to activate the immune system including Gram-positive peptidoglycan (PG) and lipoteichoic acid (LTA). In addition to these standard toxins, other bacterial components can induce inflammation. These molecules activate different signaling pathways and produce different physiological responses which can be taken advantage of for sepsis modeling. Endotoxemia modeling can provide information on pathways to inflammation in sepsis and contribute to preclinical drug development.

Auricular acupuncture (AA) is known to be effective in treatment of various pain conditions, but still there have been no randomized controlled studies of AA for treatment of acute postoperative pain. Therefore we tested whether AA of specific points is superior to sham acupuncture for complementary analgesia after total hip arthroplasty in a patient-anesthesiologist-evaluator-analyst blinded study. The patients were randomly allocated to receive true AA (lung, shenmen, thalamus and hip points) or sham procedure (4 non-acupuncture points on the auricular helix). Permanent press AA needles were retained in situ 3 days after surgery. Postoperative pain was treated with intravenous piritramide (opioid receptor agonist with analgesic potency of 0.7 compared with morphine) using a patient-controlled analgesia (PCA) pump. The time to the first analgesic request, the amount of postoperative piritramide via PCA and pain intensity on a 100-mm visual analogue scale (VAS-100) were used to evaluate postoperative analgesia. Intraoperative anesthetic requirement, incidence of analgesia-related side effects, inflammation parameters and success of patients' blinding were also recorded. Fifty-four patients (29 AA and 25 controls) completed the study. Piritramide requirement during 36 h after surgery in AA group was lower than in control: 37+/-18 vs. 54+/-21 mg; mean+/-SD; P=0.004. Pain intensity on VAS-100 and incidence of analgesia-related side effects were similar in both groups. The differences between the groups as regard patients' opinions concerning success of blinding were not significant. Findings from our study demonstrate that AA could be used to reduce postoperative analgesic requirement.

G protein-coupled receptor 55 (GPR55) shares numerous cannabinoid ligands with CB1 and CB2 receptors despite low homology with those classical cannabinoid receptors. The pharmacology of GPR55 is not yet fully elucidated; however, GPR55 utilizes a different signaling system and downstream cascade associated with the receptor. Therefore, GPR55 has emerged as a putative “type 3” cannabinoid receptor, establishing a novel class of cannabinoid receptor. Furthermore, the recent evidence of GPR55-CB1 and GPR55-CB2 heteromerization along with its broad distribution from central nervous system to peripheries suggests the importance of GPR55 in various cellular processes and pathologies and as a potential therapeutic target in inflammation.

Summary: The number of publications on the peri‐operative use of auricular acupuncture has rapidly increased within the last decade. The aim was to evaluate clinical evidence on the efficacy of auricular acupuncture for postoperative pain control. Electronic databases: Medline, MedPilot, DARE, Clinical Resource, Scopus and Biological Abstracts were searched from their inception to September 2007. All randomised clinical trials on the treatment of postoperative pain with auricular acupuncture were considered and their quality was evaluated using the Jadad scale. Pain intensity and analgesic requirements were defined as the primary outcome measures. Of 23 articles, nine fulfilled the inclusion criteria. Meta‐analytic approach was not possible because of the heterogeneity of the primary studies. In eight of the trials, auricular acupuncture was superior to control conditions. Seven randomised clinical trials scored three or more points on the Jadad scale but none of them reached the maximum of 5 points. The evidence that auricular acupuncture reduces postoperative pain is promising but not compelling.