Terlipressin in the treatment of late phase catecholamine-resistant septic shock.

BACKGROUND/AIMS: Norepinephrine, but also dopamine and epinephrine are recommended as first line vasopressors in the treatment of septic shock. In some patients, septic shock deteriorates and becomes to be resistant to catecholamines. In this situation, addition of vasopressin or terlipressin can be advantageous. The aim of our pilot study was to evaluate the impact of terlipressin on open label norepinephrine requirements and mortality. METHODOLOGY: In a randomized, controlled, single centre study we assigned patients with late advanced septic shock refractory to catecholamines (norepinephrine >0.6µg/kg/min for more than 24h) to receive either continuously terlipressin 4mg/24h for 72 hours in addition to open label norepinephrine (TERLI group) or to continue therapy only with catecholamines (CON group). All vasopressor infusions were titrated to maintain a target blood pressure. RESULTS: We enrolled 30 patients, of whom 13 were assigned to terlipressin and in 17 we continued in catecholamine therapy. There was no significant difference in norepinephrine consumption between the groups. Open label norepinephrine infusion rates decreased significantly in the TERLI group as compared with initial consumption, but the decrease we observed only in 7 (54%) patients. There was no significant difference between groups in the rate of death at day 28 (77% in TERLI group and 94% in CON group; p=0.18) or at day 90 (91% vs. 94%; p=0.85). CONCLUSIONS: Continuous terlipressin infusion was not effective in reducing norepinephrine consumption or in the mortality of patients, if administered in late phase of catecholamine refractory septic shock.

New fibrillin gene mutation - possible cause of ascending aortic dilation in patients with aortic valve disease: Preliminary results.

BACKGROUND: Approximately 10% of patients who undergo surgery for aortic valve disease (stenosis or regurgitation) suffer from ascending aortic dilation (AAD). A possible genetic etiology of AAD associated with aortic valve disease has been repeatedly mentioned in the literature, but a specific responsible gene mutation has not been described. METHODS: In the present study, two groups of patients were compared, all of whom underwent surgery for aortic valve disease. Group A was a cohort of 27 patients who suffered from aortic valve disease associated with AAD. Group B was a cohort of 29 patients with structural aortic valve disease, but without concomitant AAD (control group). Genomic DNA was extracted from the white blood cells of peripheral blood samples and was amplified using primers specific for chosen exons of the fibrillin-1 gene, including their intron/exon boundaries. Exons 26 and 27 were selected for analysis. RESULTS: Analysis of the intronic part situated close to exon 27 showed insertion of cytosine between nucleotide 37 682 and 37 683 of query sequence. This insertions was classified as IVS 37 682 and 37 683insC. This mutation was found in all 27 patients from group A (patients with structural aortic valve disease accompanied by significant AAD). The abovementioned mutation was not found in any of the 29 patients from group B. CONCLUSIONS: This finding has potential implications for risk stratification and therapeutic targeting not only for patients with existing disease, but also for the general population. Future studies are needed to determine the clinical utility of the finding; however, the present hypothesis needs to be verified by further molecular studies.