H.-J. Dieterich

Fatal outcome during anaesthesia induction in a patient with amiodarone-induced thyrotoxicosis

which was significantly different (P , 0.01, Wilcoxon rank sum test) from the treatment group. Cancer (22 patients), primary sepsis (15 patients), multiple trauma (11 patients), intracranial bleeding (11 patients), subarachnoid haemorrhage (11 patients) and aortic aneurysm rupture/repair (11 patients) were among the more common admission diagnosis in patients with adrenal and relative adrenal insufficiency. Patients with a history of hypertension, coronary artery disease, diabetes mellitus, chronic obstructive pulmonary disease and/or vascular disease seem to be at higher risk for these conditions although our study size was too small for logistic regression analysis. Etomidate use for intubation could be identified in only one patient. Overall, our findings support the notion that adrenal insufficiency diagnosed with a 1-mg cosyntropin test is common in surgical patients with volume refractory shock and responsive to hydrocortisone substitution independent of confirmed sepsis. Larger scale epidemiologic and prospective studies are warranted to determine whether patients should be routinely tested with low-dose or high-dose cosyntropin tests or empirically treated with hydrocortisone and classified as clinical responders or non-responders after 24 h.

Release of S (+) enantiomers in breath samples after anaesthesia with isoflurane racemate

Background and objective: Isoflurane is a chiral volatile anaesthetic, routinely administered as racemate. It has a low metabolic rate and is mostly eliminated via respiration. In blood samples, S(+) enantiomers are found in greater proportion in the days immediately after administration of isoflurane racemate whereas the ratio in breath samples is unknown. Methods: Breath and blood samples were drawn immediately after recovery and daily up to 19 days after operation from patients undergoing anaesthesia with isoflurane racemate. The percentage of isoflurane enantiomer was determined by gas chromatography mass spectrometry in blood and thermodesorption gas chromatography mass spectrometry in breath samples. Results: In breath samples, there were significant differences in S(+) enantiomers at all time points compared to the racemate. During the early postoperative phase, the percentage of S(+) enantiomers were significantly enhanced whereas 5 days after surgery predominantly R(−) enantiomers (50.41%) were detected in the breath samples. Also in blood samples a statistical significant accumulation of the S(+) enantiomer was noted between days 1 and 5 compared to isoflurane racemate blood control. S(+) enantiomers were significantly higher in blood compared to breath samples and was most evident on the third day after surgery (51.43%). Conclusions: During the first days after application of isoflurane racemate, the percentage of S(+) enantiomers are higher in breath and blood samples of patients. We suggest that resorbtion and/or redistribution of enantiomers are responsible for the different kinetics of isoflurane enantiomers.

LPS activation of leukocytes attenuates adhesion to endothelial cells under shear stress

Leukocyte adhesion is triggered by upregulation of cell surface adhesion molecules and counteracted by the shear forces of the flowing blood. Since both factors, inflammatory response and flow dynamics are severely altered during endotoxemia, we studied the effects of endotoxin on leukocyte–endothelial interactions under different levels of shear stress in vitro. In order to perform the experiments at precisely adjustable levels of shear stress, we used a parallel plate flow chamber as has been employed in a number of adhesion studies previously. Within this chamber, endothelial cells (HUVEC) could be perfused with neutrophils (PMN) at 0.25–3 dynes/cm2. FACS analysis of adhesion molecules, trypan blue exclusion and PMN migration showed that the cells were not altered during cell separation. To determine the effects of lipopolysaccharide (LPS) on shear-dependent adhesion, we studied HUVEC and PMN in a native state and following activation with LPS at 100 ng/ml and 10 ng/ml. All flow experiments were videotaped and the results were analysed by the paired t-test (P < 0.05). The effects of LPS on leukocyte–endothelial interactions strongly depended on the site of activation. Whereas LPS pretreatment of HUVEC increased PMN adhesion by 5–10 fold, pre-activation of the PMN resulted in a 50% reduction of adherent cells. In addition, after pre-activation of PMN, adhesion became increasingly dependent on shear stress and, thus, inhibition by LPS was most pronounced at a normal, postcapillary shear stress of 2–3 dynes/cm2. As demonstrated by addition of antibodies against selectins, the effect of LPS was due to a functional loss of L-Selectin and P-Selectin mediated interactions. In addition, integrin-mediated adhesion was impaired despite upregulation of CD11b on activated PMN. In summary, our results show that leukocyte–endothelial interactions become increasingly dependent on shear stress as soon as PMN are activated. Once PMN have undergone LPS activation, leukocyte tethering to the endothelium becomes entirely dependent on endothelial E-Selectin. Furthermore, adhesion efficiency decreases despite upregulated expression of CD11b. Since LPS increased the rigidity of PMN, it seems that the increased stiffness attenuated PMN adhesion by hampering PMN flattening and, thereby, reducing the number of available bonds to the endothelium.