Liver dysfunction affects a variety of metabolic pathways in the critically ill, but mechanisms remain poorly understood. We prospectively assessed markers of hepatic injury and function in sepsis and I/R injury in vivo and molecular mechanisms in human liver tissue ex vivo. Markers of hepatocellular injury, synthesis, and excretion, including plasma disappearance rate of indocyanine green (ICG), were measured in 48 patients with severe sepsis. Incidence of liver dysfunction was 42% as assessed by hyperbilirubinemia but 74% by impaired dye excretion. Conventional markers for liver injury failed to predict outcome, whereas dye excretion of less than 8% per minute predicted death with high sensitivity and specificity. Potential mechanisms were assessed via (a) gene expression analysis of transporter proteins for bilirubin and ICG in cultured human liver tissue, and (b) monitoring uptake and excretion of the dye after I/R injury in 12 patients receiving a biliary T-tube during liver transplantation. Ex vivo gene expression of transporters was differentially affected for bilirubin and ICG with upregulation of basolateral and downregulation of canalicular ICG transporters. Consistently, patients with unfavorable course after liver transplantation displayed almost complete cessation of biliary dye excretion, whereas uptake into the hepatocyte was reduced by only 40%. In conclusion, standard liver tests lack the required sensitivity to assess hepatic injury and function in the critically ill. Dye excretion better reflects excretory and/or microvascular dysfunction but still underestimates impaired canalicular transport. The observed differential susceptibility of the polar surfaces of human hepatocytes has potential implications for monitoring liver function and drug-induced liver injury.

We investigated the specificity for gram-negative stimuli as well as the contribution of signal transduction pathways for leukocyte hyporesponsiveness in sepsis or following cardiopulmonary bypass (CPB). Whole blood of nine patients undergoing CPB and 25 patients with severe sepsis was stimulated ex vivo with LPS (E. coli O111:B4) or with Staphylococcus aureus Cowan strain I (SAC-I) lysate in the absence or presence of inhibitors of protein kinase C (PKC), protein-tyrosine kinase (PTK), or protein-tyrosine phosphatase (PTP). Both toxins stimulated a TNF-alpha response through PTK signaling. Although suppression of the cytokine response was similar for LPS and SAC-I after CPB, it was significantly more pronounced for SAC-I in sepsis. Inhibition of PTP failed to increase TNF-alpha upon LPS, whereas a moderate increase was observed with SAC-I. Impaired TNF-alpha responses occur in sepsis and after CPB. Although this has primarily been reported for gram-negative stimuli, our data suggest that this is even more pronounced for gram-positive stimuli in severe sepsis. Although PTK was the predominant signaling pathway, inhibition of PTP only partially restored the TNF-alpha response to SAC-I. Our results suggest that cellular mechanisms underlying monocyte deactivation are different in sepsis or following CPB and are discriminate for gram-positive and gram-negative toxins.

The effect of intra-articular bupivacaine on postoperative pain following arthroscopy has been intensively studied for the knee joint but no data are currently available for the hip joint. The aim of the present prospective, randomized and double-blind study was to evaluate a possible effect of intra-articular bupivacaine on postoperative pain intensity following hip arthroscopy. A total of 26 patients were included: 13 received 20 ml of 0.25% bupivacaine through the trocar at the end of surgery and 13 patients received 20 ml of 0.9% NaCl as placebo. Postoperative pain intensity was assessed using a visual analogue scale (VAS) at 0.5 h, 4 h, 8 h, 12 h, 16 h and 20 h, at rest and during movement of the joint and on the basis of additional piritramide requirements. Furthermore, a mean VAS was calculated as the arithmetic mean of all VAS scores assessed over the whole study period. In the bupivacaine group, a significantly lower mean VAS was recorded at rest (17.5 vs 27.5, p=0.05) and during movement of the hip joint (23 vs. 46, p=0.001). The additional piritramide consumption tended to be higher in the placebo group. In conclusion, intra-articular bupivacaine following arthroscopic hip surgery reduces pain in the postoperative period mainly during movement and thus may possibly allow earlier mobilization.

Severe sepsis leads to a substantial suppression of stimulated cytokine response. Prolonged suppression may serve as a marker of unfavourable outcome in male but not in female individuals suffering from severe sepsis. Furthermore, our data suggest that gender differences in cellular immunity described for young, sexually mature animals obviously persist in typical postmenopausal intensive care unit patients, although a direct interaction between testosterone or estradiol and LPS-stimulated cytokine response could not be demonstrated.

The intubation conditions after Roc were significantly better in women than in men. The differences were Roc-related and did not occur in the control groups.