A non-interventional comparative study of the 20:1 combination of cafedrine/theodrenaline versus ephedrine for the treatment of intra-operative arterial hypotension: the ‘HYPOTENS’ study design and rationale

<p><b>Objective:</b> To compare the effectiveness of 20:1 cafedrine/theodrenaline approved for use in Germany to ephedrine in the restoration of arterial blood pressure and on post-operative outcomes in patients with intra-operative arterial hypotension of any origin under standard clinical practice conditions.</p> <p><b>Methods and results:</b> ‘HYPOTENS’ is a national, multi-center, prospective, open-label, two-armed, non-interventional study. Effectiveness and post-operative outcome following cafedrine/theodrenaline or ephedrine therapy will be evaluated in two cohorts of hypotensive patients. Cohort A includes patients aged ≥50 years with ASA-classification 2–4 undergoing non-emergency surgical procedures under general anesthesia. Cohort B comprises patients undergoing Cesarean section under spinal anesthesia. Participating surgical departments will be assigned to a treatment arm by routinely used anti-hypotensive agent. To minimize bias, matched department pairs will be compared in a stratified selection process. The composite primary end-point is the lower absolute deviation from individually determined target blood pressure (IDTBP) and the incidence of heart rate ≥100 beats/min in the first 15 min. Secondary end-points include incidence and degree of early post-operative delirium (cohort A), severity of fetal acidosis in the newborn (cohort B), upper absolute deviation from IDTBP, percentage increase in systolic blood pressure, and time to IDTBP.</p> <p><b>Conclusion:</b> This open-label, non-interventional study design mirrors daily practice in the treatment of patients with intra-operative hypotension and ensures full treatment decision autonomy with respect to each patient’s individual condition. Selection of participating sites by a randomization process addresses bias without interfering with the non-interventional nature of the study. First results are expected in 2018. ClinicalTrials.gov identifier: NCT02893241; DRKS identifier: DRKS00010740.</p

Onset of heart failure determines the hepatic cell death pattern

Background and rationale. Acute and chronic heart failure (HF) may affect the liver, but the underlying mechanisms that lead to progressive liver damage are poorly understood. The hepatic cytokeratin-18 (CK18) epitopes M65 and M30 have been reported to distinguish between overall (necrotic) and apoptotic cell death, respectively. We aimed to evaluate the predominant hepatic cell death pattern in acute vs. chronic heart failure and examined if these assays predict the course of the disease.Main results. In a prospective study comprising 21 patients with acute HF (AHF) and 18 patients with chronic HF (CHF) serum levels of M65 and M30 were assessed. Compared with CHF, M65 levels were significantly increased in patients with AHF (CHF: 1,283 ± 591.6U/l vs. AHF: 20,912 ± 15,132U/l, p > 0.001). In addition, M30 levels were significantly increased in AHF (CHF: 642.2 ± 177.4U/l vs. AHF: 3,844 ± 5,293U/l, p < 0.05), but the M30/M65 ratio was significantly higher in CHF (CHF: 0.54 ± 0.15 vs. AHF: 0.20 ± 0.19, p < 0.001), indicating a greater contribution of apoptotic cell death in CHF. AHF patients with higher M30 values had a worse prognosis.Conclusions. The ratio of CK18 M30/M65 is a potential marker to discriminate AHF from CHF induced LF and M30 might be a prognostic marker for survival in AHF induced liver injury